Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practices and Related Regulations for Blood and Blood Components; and Requirements for Donor Testing, Donor Notification, and “Lookback”, 11444-11449 [2015-04381]
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should also contain information on
analytical methodology for the nutrient
that is the subject of a claim based on
an authoritative statement. We intend to
review the notifications we receive to
ensure that they comply with the
criteria established by the FD&C Act.
In the Federal Register of November
21, 2014 (79 FR 69494), FDA published
a 60-day notice requesting public
comment on the proposed collection of
information. No comments were
received in response to the notice.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
responses per
respondent
Number of
respondents
Section of the FD&C Act
Average
burden per
response
Total annual
responses
Total hours
403(r)(2)(G) (nutrient content claims) ..................................
403(r)(2)(C) (health claims) .................................................
Guidance for notifications ....................................................
1
1
2
1
1
1
1
1
2
250
450
1
250
450
2
Total ..............................................................................
........................
........................
........................
........................
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1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
These estimates are based on our
experience with health claims, nutrient
content claims, and other similar
notification procedures that fall under
our jurisdiction. To avoid estimating the
number of respondents as zero, we
estimate that there will be one or fewer
respondents annually for nutrient
content claim and health claim
notifications. We estimate that we will
receive one nutrient content claim
notification and one health claim
notification per year over the next 3
years.
Section 403(r)(2)(G) and (r)(3)(C) of
the FD&C Act requires that the
notification include the exact words of
the claim, a copy of the authoritative
statement, a concise description of the
basis upon which such person relied for
determining that this is an authoritative
statement as outlined in the FD&C Act,
and a balanced representation of the
scientific literature relating to the
relationship between a nutrient and a
disease or health-related condition to
which a health claim refers or to the
nutrient level to which the nutrient
content claim refers. This balanced
representation of the scientific literature
is expected to include a bibliography of
the scientific literature on the topic of
the claim and a brief, balanced account
or analysis of how this literature either
supports or fails to support the
authoritative statement.
Since the claims are based on
authoritative statements of a scientific
body of the U.S. Government or NAS,
we believe that the information that is
required by the FD&C Act to be
submitted with a notification will be
readily available to a respondent.
However, the respondent will have to
collect and assemble that information.
Based on communications with firms
that have submitted notifications, we
estimate that one respondent will take
250 hours to collect and assemble the
information required by the statute for
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a nutrient content claim notification.
Further, we estimate that one
respondent will take 450 hours to
collect and assemble the information
required by the statute for a health claim
notification.
Under the guidance, notifications
should also contain information on
analytical methodology for the nutrient
that is the subject of a claim based on
an authoritative statement. The
guidance applies to both nutrient
content claim and health claim
notifications. We have determined that
this information should be readily
available to a respondent and, thus, we
estimate that it will take a respondent 1
hour to incorporate the information into
each notification. We expect there will
be two respondents for a total of 2
hours.
Dated: February 24, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015–04380 Filed 3–2–15; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2005–N–0161]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Current Good
Manufacturing Practices and Related
Regulations for Blood and Blood
Components; and Requirements for
Donor Testing, Donor Notification, and
‘‘Lookback’’
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
SUMMARY:
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that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by April 2,
2015.
To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, FAX:
202–395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0116. Also
include the FDA docket number found
in brackets in the heading of this
document.
ADDRESSES:
FDA
PRA Staff, Office of Operations, Food
and Drug Administration, 8455
Colesville Rd., COLE–14526, Silver
Spring, MD 20993–0002, PRAStaff@
fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
Current Good Manufacturing Practices
and Related Regulations for Blood and
Blood Components; and Requirements
for Donor Testing, Donor Notification,
and ‘‘Lookback’’—(OMB Control
Number 0910–0116)—Extension
All blood and blood components
introduced or delivered for introduction
into interstate commerce are subject to
section 351(a) of the Public Health
Service Act (PHS Act) (42 U.S.C.
262(a)). Section 351(a) requires that
manufacturers of biological products,
which include blood and blood
components intended for further
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manufacture into injectable products,
have a license, issued upon a
demonstration that the product is safe,
pure, and potent and that the
manufacturing establishment meets all
applicable standards, including those
prescribed in the FDA regulations
designed to ensure the continued safety,
purity, and potency of the product. In
addition, under section 361 of the PHS
Act (42 U.S.C. 264), by delegation from
the Secretary of Health and Human
Services, FDA may make and enforce
regulations necessary to prevent the
introduction, transmission, or spread of
communicable diseases from foreign
countries into the States or possessions,
or from one State or possession into any
other State or possession.
Section 351(j) of the PHS Act states
that the Federal Food, Drug, and
Cosmetic (FD&C) Act also applies to
biological products. Blood and blood
components for transfusion or for
further manufacture into injectable
products are drugs, as that term is
defined in section 201(g)(1) of the FD&C
Act (21 U.S.C. 321(g)(1)). Because blood
and blood components are drugs under
the FD&C Act, blood and plasma
establishments must comply with the
substantive provisions and related
regulatory scheme of the FD&C Act. For
example, under section 501 of the FD&C
Act (21 U.S.C. 351(a)), drugs are deemed
‘‘adulterated’’ if the methods used in
their manufacturing, processing,
packing, or holding do not conform to
current good manufacturing practice
(CGMP) and related regulations.
The CGMP regulations for blood and
blood components (21 CFR part 606)
and related regulations implement
FDA’s statutory authority to ensure the
safety, purity, and potency of blood and
blood components. The public health
objective in testing human blood donors
for evidence of infection due to
communicable disease agents and in
notifying donors is to prevent the
transmission of communicable disease.
For example, the ‘‘lookback’’
requirements are intended to help
ensure the continued safety of the blood
supply by providing necessary
information to users of blood and blood
components and appropriate
notification of recipients of transfusion
who are at increased risk for
transmitting human immunodeficiency
virus (HIV) or hepatitis C virus (HCV)
infection.
The information collection
requirements in the CGMP, donor
testing, donor notification, and
‘‘lookback’’ regulations provide FDA
with the necessary information to
perform its duty to ensure the safety,
purity, and potency of blood and blood
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components. These requirements
establish accountability and traceability
in the processing and handling of blood
and blood components and enable FDA
to perform meaningful inspections.
The recordkeeping requirements serve
preventive and remedial purposes. The
third-party disclosure requirements
identify the various blood and blood
components and important properties of
the product, demonstrate that the CGMP
requirements have been met, and
facilitate the tracing of a product back
to its original source. The reporting
requirements inform FDA of certain
information that may require immediate
corrective action.
Under the reporting requirements,
§ 606.170(b), in brief, requires that
facilities notify FDA’s Center for
Biologics Evaluation and Research
(CBER), as soon as possible after
confirming a complication of blood
collection or transfusion to be fatal. The
collecting facility is to report donor
fatalities, and the compatibility testing
facility is to report recipient fatalities.
The regulation also requires the
reporting facility to submit a written
report of the investigation within 7 days
after the fatality. In fiscal year 2013,
FDA received 72 of these reports.
Section 610.40(g)(2) (21 CFR
610.40(g)(2)) requires an establishment
to obtain written approval from FDA to
ship human blood or blood components
for further manufacturing use prior to
completion of testing for evidence of
infection due to certain communicable
disease agents.
Section 610.40(h)(2)(ii)(A), in brief,
requires an establishment to obtain
written approval from FDA to use or
ship human blood or blood components
found to be reactive by a screening test
for evidence of certain communicable
disease agent(s) or collected from a
donor with a record of a reactive
screening test.
Under the third-party disclosure
requirements, § 610.40(c)(1)(ii), in brief,
requires that each donation dedicated to
a single identified recipient be labeled
as required under § 606.121 and with a
label containing the name and
identifying information of the recipient.
The information collection requirements
under § 606.121 are part of usual and
customary business practice.
Sections 610.40(h)(2)(ii)(C) and
(h)(2)(ii)(D), in brief, require an
establishment to label certain reactive
human blood and blood components
with the appropriate screening test
results, and, if they are intended for
further manufacturing use into
injectable products, to include a
statement on the label indicating the
exempted use specifically approved by
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11445
FDA. Also, § 610.40(h)(2)(vi) requires
each donation of human blood or blood
components, excluding Source Plasma,
that tests reactive by a screening test for
syphilis and is determined to be a
biological false positive to be labeled
with both test results.
Section 610.42(a) requires a warning
statement ‘‘indicating that the product
was manufactured from a donation
found to be reactive by a screening test
for evidence of infection due to the
identified communicable disease
agent(s)’’ in the labeling for medical
devices containing human blood or a
blood component found to be reactive
by a screening test for evidence of
infection due to a communicable
disease agent(s) or syphilis.
In brief, §§ 610.46 and 610.47 require
blood collecting establishments to
establish, maintain, and follow an
appropriate system for performing HIV
and HCV prospective ‘‘lookback’’ when:
(1) A donor tests reactive for evidence
of HIV or HCV infection or (2) the
collecting establishment becomes aware
of other reliable test results or
information indicating evidence of HIV
or HCV infection (prospective
‘‘lookback’’) (see §§ 610.46(a)(1) and
610.47(a)(1)). The requirement for ‘‘an
appropriate system’’ requires the
collecting establishment to design
standard operating procedures (SOPs) to
identify and quarantine all blood and
blood components previously collected
from a donor who later tests reactive for
evidence of HIV or HCV infection, or
when the collecting establishment is
made aware of other reliable test results
or information indicating evidence of
HIV or HCV infection. Within 3
calendar days of the donor testing
reactive by an HIV or HCV screening
test or the collecting establishment
becoming aware of other reliable test
results or information, the collecting
establishment must, among other things,
notify consignees to quarantine all
identified previously collected in-date
blood and blood components
(§§ 610.46(a)(1)(ii)(B) and
610.47(a)(1)(ii)(B)) and, within 45 days,
notify the consignees of supplemental
test results, or the results of a reactive
screening test if there is no available
supplemental test that is approved for
such use by FDA (§§ 610.46(a)(3) and
610.47(a)(3)).
Consignees also must establish,
maintain, and follow an appropriate
system for performing HIV and HCV
‘‘lookback’’ when notified by the
collecting establishment that they have
received blood and blood components
previously collected from donors who
later tested reactive for evidence of HIV
or HCV infection, or when the collecting
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establishment is made aware of other
reliable test results or information
indicating evidence of HIV or HCV
infection in a donor (§§ 610.46(b) and
610.47(b)). This provision for a system
requires the consignee to establish SOPs
for, among other things, notifying
transfusion recipients of blood and
blood components, or the recipient’s
physician of record or legal
representative, when such action is
indicated by the results of the
supplemental (additional, more specific)
tests or a reactive screening test if there
is no available supplemental test that is
approved for such use by FDA, or if
under an investigational new drug
application (IND) or an investigational
device exemption (IDE), is exempted for
such use by FDA. The consignee must
make reasonable attempts to perform the
notification within 12 weeks of receipt
of the supplemental test result or receipt
of a reactive screening test result when
there is no available supplemental test
that is approved for such use by FDA,
or if under an IND or IDE, is exempted
for such use by FDA (§§ 610.46(b)(3)
and 610.47(b)(3)).
Section 630.6(a) (21 CFR 630.6(a))
requires an establishment to make
reasonable attempts to notify any donor
who has been deferred as required by
§ 610.41, or who has been determined
not to be eligible as a donor. Section
630.6(d)(1) requires an establishment to
provide certain information to the
referring physician of an autologous
donor who is deferred based on the
results of tests as described in § 610.41.
Under the recordkeeping
requirements, § 606.100(b), in brief,
requires that written SOPs be
maintained for all steps to be followed
in the collection, processing,
compatibility testing, storage, and
distribution of blood and blood
components used for transfusion and
further manufacturing purposes. Section
606.100(c) requires the review of all
records pertinent to the lot or unit of
blood prior to release or distribution.
Any unexplained discrepancy or the
failure of a lot or unit of final product
to meet any of its specifications must be
thoroughly investigated, and the
investigation, including conclusions
and followup, must be recorded.
In brief, § 606.110(a) provides that the
use of plateletpheresis and
leukapheresis procedures to obtain a
product for a specific recipient may be
at variance with the additional
standards for that specific product if,
among other things, the physician
certifies in writing that the donor’s
health permits plateletpheresis or
leukapheresis. Section 606.110(b)
requires establishments to request prior
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approval from CBER for plasmapheresis
of donors who do not meet donor
requirements. The information
collection requirements for § 606.110(b)
are approved under OMB control
number 0910–0338 and, therefore, are
not reflected in tables 1 and 2.
Section 606.151(e) requires that SOPs
for compatibility testing include
procedures to expedite transfusion in
life-threatening emergencies; records of
all such incidents must be maintained,
including complete documentation
justifying the emergency action, which
must be signed by a physician.
So that each significant step in the
collection, processing, compatibility
testing, storage, and distribution of each
unit of blood and blood components can
be clearly traced, § 606.160 requires that
legible and indelible contemporaneous
records of each such step be made and
maintained for no less than 10 years.
Section 606.160(b)(1)(viii) requires
records of the quarantine, notification,
testing and disposition performed under
the HIV and HCV ‘‘lookback’’
provisions. Furthermore,
§ 606.160(b)(1)(ix) requires a blood
collection establishment to maintain
records of notification of donors
deferred or determined not to be eligible
for donation, including appropriate
followup. Section 606.160(b)(1)(xi)
requires an establishment to maintain
records of notification of the referring
physician of a deferred autologous
donor, including appropriate followup.
Section 606.165, in brief, requires that
distribution and receipt records be
maintained to facilitate recalls, if
necessary.
Section 606.170(a) requires records to
be maintained of any reports of
complaints of adverse reactions arising
as a result of blood collection or
transfusion. Each such report must be
thoroughly investigated, and a written
report, including conclusions and
followup, must be prepared and
maintained. Section 606.170(a) also
requires that when an investigation
concludes that the product caused the
transfusion reaction, copies of all such
written reports must be forwarded to
and maintained by the manufacturer or
collecting facility.
Section 610.40(g)(1) requires an
establishment to appropriately
document a medical emergency for the
release of human blood or blood
components prior to completion of
required testing.
In addition to the CGMP regulations
in part 606, there are regulations in 21
CFR part 640 that require additional
standards for certain blood and blood
components as follows: Sections
640.3(a)(1), (a)(2), and (f); 640.4(a)(1)
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and (a)(2); 640.25(b)(4) and (c)(1);
640.27(b); 640.31(b); 640.33(b);
640.51(b); 640.53(b) and (c); 640.56(b)
and (d); 640.61; 640.63(b)(3), (e)(1), and
(e)(3); 640.65(b)(2); 640.66; 640.71(b)(1);
640.72; 640.73; and 640.76(a) and (b).
The information collection requirements
and estimated burdens for these
regulations are included in the part 606
burden estimates, as described in tables
1 and 2.
Respondents to this collection of
information are licensed and unlicensed
blood establishments that collect blood
and blood components, including
Source Plasma and Source Leukocytes,
inspected by FDA, and other transfusion
services inspected by Centers for
Medicare and Medicaid Services (CMS).
Based on information received from
CBER’s database systems, there are
approximately 416 licensed Source
Plasma establishments with multiple
locations and approximately 1,265
licensed blood collection
establishments, for an estimated total of
1,681 licensed blood collection
establishments. Also, there are an
estimated total of 680 unlicensed,
registered blood collection
establishments for an approximate total
of 2,361 collection establishments (416
+ 1,265 + 680 = 2,361 establishments).
Of these establishments, approximately
990 perform plateletpheresis and
leukapheresis. These establishments
annually collect approximately 40
million units of Whole Blood and blood
components, including Source Plasma
and Source Leukocytes, and are
required to follow FDA ‘‘lookback’’
procedures. In addition, there are
another 4,961 establishments that fall
under the Clinical Laboratory
Improvement Amendments of 1988
(CLIA) (Pub. L. 100–578) (formerly
referred to as facilities approved for
Medicare reimbursement) that transfuse
blood and blood components.
The following reporting and
recordkeeping estimates are based on
information provided by industry, CMS,
and FDA experience. Based on
information received from industry, we
estimate that there are approximately 25
million donations of Source Plasma
from approximately 2 million donors
and approximately 15 million donations
of Whole Blood, including
approximately 225,000 (approximately
1.5 percent of 15 million) autologous
donations, from approximately 10.9
million donors. Assuming each
autologous donor makes an average of 2
donations, FDA estimates that there are
approximately 112,500 autologous
donors.
FDA estimates that approximately 5
percent (3,600) of the 72,000 donations
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that are donated specifically for the use
of an identified recipient would be
tested under the dedicated donors’
testing provisions in § 610.40(c)(1)(ii).
Under §§ 610.40(g)(2) and
(h)(2)(ii)(A), Source Leukocytes, a
licensed product that is used in the
manufacture of interferon, which
requires rapid preparation from blood,
is currently shipped prior to completion
of testing for evidence of certain
communicable disease agents.
Shipments of Source Leukocytes are
preapproved under a biologics license
application (BLA) and each shipment
does not have to be reported to the
Agency. Based on information from
CBER’s database system, FDA receives
less than one application per year from
manufacturers of Source Leukocytes.
However, for calculation purposes, we
are estimating one application annually.
Under §§ 610.40(h)(2)(ii)(C) and
(h)(2)(ii)(D), FDA estimates that each
manufacturer would ship an estimated 1
unit of human blood or blood
components per month (12 per year)
that would require two labels; one as
reactive for the appropriate screening
test under § 610.40(h)(2)(ii)(C), and the
other stating the exempted use
specifically approved by FDA under
§ 610.40(h)(2)(ii)(D). According to
CBER’s database system, there are
approximately 40 licensed
manufacturers that ship known reactive
human blood or blood components.
Based on information we received
from industry, we estimate that
approximately 18,000 donations: (1)
Annually test reactive by a screening
test for syphilis; (2) are determined to be
biological false positives by additional
testing; and (3) are labeled accordingly
(§ 610.40(h)(2)(vi)).
Human blood or a blood component
with a reactive screening test, as a
component of a medical device, is an
integral part of the medical device, e.g.,
a positive control for an in vitro
diagnostic testing kit. It is usual and
customary business practice for
manufacturers to include on the
container label a warning statement that
identifies the communicable disease
agent. In addition, on the rare occasion
when a human blood or blood
component with a reactive screening
test is the only component available for
a medical device that does not require
a reactive component, then a warning
statement must be affixed to the medical
device. To account for this rare occasion
under § 610.42(a), we estimate that the
warning statement would be necessary
no more than once a year.
FDA estimates that approximately
3,500 repeat donors will test reactive on
a screening test for HIV. We also
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estimate that an average of three
components was made from each
donation. Under §§ 610.46(a)(1)(ii)(B)
and (a)(3), this estimate results in 10,500
(3,500 × 3) notifications of the HIV
screening test results to consignees by
collecting establishments for the
purpose of quarantining affected blood
and blood components, and another
10,500 (3,500 × 3) notifications to
consignees of subsequent test results.
We estimate that § 610.46(b)(3) will
require 4,961 consignees to notify
transfusion recipients, their legal
representatives, or physicians of record
an average of 0.35 times per year
resulting in a total number of 1,755 (585
confirmed positive repeat donors × 3)
notifications. Also under § 610.46(b)(3),
we estimate and include the time to
gather test results and records for each
recipient and to accommodate multiple
attempts to contact the recipient.
Furthermore, we estimate that
approximately 7,800 repeat donors per
year would test reactive for antibody to
HCV. Under §§ 610.47(a)(1)(ii)(B) and
610.47(a)(3), collecting establishments
would notify the consignee 2 times for
each of the 23,400 (7,800 × 3
components) components prepared from
these donations, once for quarantine
purposes and again with additional
HCV test results for a total of 46,800
notifications as an annual ongoing
burden. Under § 610.47(b)(3), we
estimate that approximately 4,961
consignees would notify approximately
2,050 recipients or their physicians of
record annually.
Based on industry estimates,
approximately 13 percent of
approximately 10 million potential
donors (1.3 million donors) who come
to donate annually are determined not
to be eligible for donation prior to
collection because of failure to satisfy
eligibility criteria. It is the usual and
customary business practice of
approximately 1,945 (1,265 + 680) blood
collecting establishments to notify
onsite and to explain why the donor is
determined not to be suitable for
donating. Based on such available
information, we estimate that two-thirds
(1,297) of the 1,945 blood collecting
establishments provided onsite
additional information and counseling
to a donor determined not to be eligible
for donation as usual and customary
business practice. Consequently, we
estimate that only one-third, or 648,
approximately, blood collecting
establishments would need to provide,
under § 630.6(a), additional information
and onsite counseling to the estimated
433,333 (one-third of approximately 1.3
million) ineligible donors.
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11447
It is estimated that another 4.5 percent
of 10 million potential donors (450,000
donors) are deferred annually based on
test results. We estimate that
approximately 95 percent of the
establishments that collect 99 percent of
the blood and blood components notify
donors who have reactive test results for
HIV, Hepatitis B Virus, HCV, Human
T-Lymphotropic Virus, and syphilis as
usual and customary business practice.
Consequently, 5 percent of the 1,681
establishments (84) collecting 1 percent
(4,500) of the deferred donors (450,000)
would notify donors under § 630.6(a).
As part of usual and customary
business practice, collecting
establishments notify an autologous
donor’s referring physician of reactive
test results obtained during the donation
process required under § 630.6(d)(1).
However, we estimate that
approximately 5 percent of the 1,265
blood collection establishments (63)
may not notify the referring physicians
of the estimated 2 percent of 112,500
autologous donors with the initial
reactive test results (2,250) as their
usual and customary business practice.
The recordkeeping chart reflects the
estimate that approximately 95 percent
of the recordkeepers, which collect 99
percent of the blood supply, have
developed SOPs as part of their
customary and usual business practice.
Establishments may minimize burdens
associated with CGMP and related
regulations by using model standards
developed by industries’ accreditation
organizations. These accreditation
organizations represent almost all
registered blood establishments.
Under § 606.160(b)(1)(ix), we estimate
the total annual records based on the
approximately 1.3 million donors
determined not to be eligible to donate
and each of the estimated 1.75 million
(1.3 million + 450,000) donors deferred
based on reactive test results for
evidence of infection because of
communicable disease agents. Under
§ 606.160(b)(1)(xi), only the 1,945
registered blood establishments collect
autologous donations and, therefore, are
required to notify referring physicians.
We estimate that 4.5 percent of the
112,500 autologous donors (5,063) will
be deferred under § 610.41, which in
turn will lead to the notification of their
referring physicians.
FDA has concluded that the use of
untested or incompletely tested but
appropriately documented human blood
or blood components in rare medical
emergencies should not be prohibited.
We estimate the recordkeeping under
§ 610.40(g)(1) to be minimal with one or
fewer occurrences per year. The
reporting of test results to the consignee
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Federal Register / Vol. 80, No. 41 / Tuesday, March 3, 2015 / Notices
in § 610.40(g) is part of the usual and
customary business practice or
procedure to finish the testing and
provide the results to the manufacturer
responsible for labeling the blood
products.
The average burden per response
(hours) and average burden per
recordkeeping (hours) are based on
estimates received from industry or FDA
experience with similar reporting or
recordkeeping requirements.
In the Federal Register of October 20,
2014 (79 FR 62629), FDA published a
60-day notice requesting public
comment on the proposed collection of
information. FDA received five
comments; however, the comments
were not responsive to the comment
request on the four specified aspects of
the collection of information and did
not provide any data or explanation that
would support a change regarding the
information collection estimates.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
responses per
respondent
Number of
respondents
21 CFR section
Average
burden per
response
Total annual
responses
Total hours
606.170(b) 2 ..........................................................................
610.40(g)(2) .........................................................................
610.40(h)(2)(ii)(A) .................................................................
72
1
1
1
1
1
72
1
1
20
1
1
1,440
1
1
Total ..............................................................................
........................
........................
........................
........................
1,442
1 There
2 The
are no capital costs or operating and maintenance costs associated with this collection of information.
reporting requirement in § 640.73, which addresses the reporting of fatal donor reactions, is included in the estimate for § 606.170(b).
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
21 CFR section
606.100(b) 2 .......................................
606.100(c) .........................................
606.110(a) 3 .......................................
606.151(e) .........................................
606.160 4 ...........................................
606.160(b)(1)(viii) ..............................
HIV consignee notification ................
606.160(b)(1)(viii) ..............................
HCV consignee notification ...............
HIV recipient notification ...................
HCV recipient notification .................
606.160(b)(1)(ix) ...............................
606.160(b)(1)(xi) ...............................
606.165 .............................................
606.170(a) .........................................
610.40(g)(1) ......................................
Total ...........................................
Number of
records per
recordkeeper
5 366
Total annual
records
Average burden per recordkeeping
Total hours
5 366
1,945
4,961
1,945
4,961
4,961
4,961
2,361
1,945
5 366
5 366
2,361
1
10
1
12
1,046.45
10.80
4.23
24.06
9.43
0.35
0.41
741.21
2.6
1,046.45
12
1
366
3,660
50
4,392
383,000
21,000
21,000
46,800
46,800
1,755
2,050
1,750,000
5,063
383,000
4,392
2,361
24 .....................................................
1 .......................................................
0.5 (30 minutes) ...............................
0.08 (5 minutes) ...............................
0.75 (45 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
0.05 (3 minutes) ...............................
0.05 (3 minutes) ...............................
0.08 (5 minutes) ...............................
1 .......................................................
0.5 (30 minutes) ...............................
8,784
3,660
25
351
287,250
3,570
3,570
7,956
7,956
298
349
87,500
253
30,640
4,392
1,180
........................
........................
........................
...........................................................
447,734
5 366
6 50
5 366
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
recordkeeping requirements in §§ 640.3(a)(1), 640.4(a)(1), and 640.66, which address the maintenance of SOPs, are included in the estimate for § 606.100(b).
3 The recordkeeping requirements in § 640.27(b), which address the maintenance of donor health records for the plateletpheresis, are included
in the estimate for § 606.110(a).
4 The recordkeeping requirements in §§ 640.3(a)(2) and (f); 640.4(a)(2); 640.25(b)(4) and (c)(1); 640.31(b); 640.33(b); 640.51(b); 640.53(b) and
(c); 640.56(b) and (d); 640.61; 640.63(b)(3), (e)(1), and (e)(3); 640.65(b)(2); 640.71(b)(1); 640.72; and 640.76(a) and (b), which address the
maintenance of various records, are included in the estimate for § 606.160.
5 Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 ×
4,961 + 2,361 = 366).
6 Five percent of plateletpheresis and leukapheresis establishments (0.05 × 990 = 50).
2 The
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
mstockstill on DSK4VPTVN1PROD with NOTICES
606.170(a) .........................................
610.40(c)(1)(ii) ...................................
610.40(h)(2)(ii)(C) and (h)(2)(ii)(D) ...
610.40(h)(2)(vi) .................................
610.42(a) ...........................................
610.46(a)(1)(ii)(B) ..............................
610.46(a)(3) ......................................
610.46(b)(3) ......................................
610.47(a)(1)(ii)(B) ..............................
VerDate Sep<11>2014
19:24 Mar 02, 2015
Number of
responses per
respondent
Number of
respondents
21 CFR section
Jkt 235001
2 366
2,361
40
2,361
1
1,945
1,945
4,961
1,945
PO 00000
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1.2
1.52
12
7.62
1
5.40
5.40
0.35
12.03
Fmt 4703
Total annual
responses
439
3,600
480
18,000
1
10,500
10,500
1,755
23,400
Sfmt 4703
Average burden per response
0.5 (30 minutes) ...............................
0.08 (5 minutes) ...............................
0.2 (12 minutes) ...............................
0.08 (5 minutes) ...............................
1 .......................................................
0.17 (10 minutes) .............................
0.17 (10 minutes) .............................
1 .......................................................
0.17 (10 minutes) .............................
E:\FR\FM\03MRN1.SGM
03MRN1
Total hours
220
288
96
1,440
1
1,785
1,785
1,755
3,978
Federal Register / Vol. 80, No. 41 / Tuesday, March 3, 2015 / Notices
11449
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1—Continued
Number of
responses per
respondent
Number of
respondents
21 CFR section
Total annual
responses
Average burden per response
Total hours
610.47(a)(3) ......................................
610.47(b)(3) ......................................
630.6(a) 3 ...........................................
630.6(a) 4 ...........................................
630.6(d)(1) ........................................
1,945
4,961
648
84
63
12.03
0.41
668.72
53.57
35.71
23,400
2,050
433,333
4,500
2,250
0.17 (10 minutes) .............................
1 .......................................................
0.08 (5 minutes) ...............................
1.5 (90 minutes) ...............................
1 .......................................................
3,978
2,050
34,667
6,750
2,250
Total ...........................................
........................
........................
........................
...........................................................
61,043
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 ×
4,961 + 2,361 = 366).
3 Notification of donors determined not to be eligible for donation based on failure to satisfy eligibility criteria.
4 Notification of donors deferred based on reactive test results for evidence of infection due to communicable disease agents.
2 Five
Dated: February 25, 2015.
Leslie Kux,
Associate Commissioner for Policy.
Spring, MD 20993–0002, PRAStaff@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
[FR Doc. 2015–04381 Filed 3–2–15; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2014–N–1721]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Investigational
New Drug Applications
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by April 2,
2015.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, FAX:
202–395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0014. Also
include the FDA docket number found
in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT: FDA
PRA Staff, Office of Operations, Food
and Drug Administration, 8455
Colesville Rd., COLE–14526, Silver
mstockstill on DSK4VPTVN1PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
19:24 Mar 02, 2015
Jkt 235001
Investigational New Drug (IND)
Regulations—21 CFR Part 312 (OMB
Control Number 0910–0014)—Extension
FDA is requesting OMB approval for
the reporting and recordkeeping
requirements contained in FDA
regulations entitled ‘‘Investigational
New Drug Application’’ in part 312 (21
CFR part 312). Part 312 implements
provisions of section 505(i) of the
Federal Food, Drug, and Cosmetic Act
(the FD&C Act) (21 U.S.C. 355(i)) to
issue regulations under which the
clinical investigation of the safety and
effectiveness of unapproved new drugs
and biological products can be
conducted.
FDA is charged with implementing
statutory requirements that drug
products marketed in the United States
be shown to be safe and effective,
properly manufactured, and properly
labeled for their intended uses. Section
505(a) of the FD&C Act provides that a
new drug may not be introduced or
delivered for introduction into interstate
commerce in the United States unless
FDA has previously approved a new
drug application (NDA). FDA approves
an NDA only if the sponsor of the
application first demonstrates that the
drug is safe and effective for the
conditions prescribed, recommended, or
suggested in the product’s labeling.
Proof must consist, in part, of adequate
and well-controlled studies, including
studies in humans, that are conducted
by qualified experts. The IND
regulations establish reporting
requirements that include an initial
application as well as amendments to
that application, reports on significant
PO 00000
Frm 00063
Fmt 4703
Sfmt 4703
revisions of clinical investigation plans,
and information on a drug’s safety or
effectiveness. In addition, the sponsor is
required to give FDA an annual
summary of the previous year’s clinical
experience.
Submissions are reviewed by medical
officers and other Agency scientific
reviewers assigned responsibility for
overseeing the specific study. The IND
regulations also contain recordkeeping
requirements that pertain to the
responsibilities of sponsors and
investigators. The detail and complexity
of these requirements are dictated by the
scientific procedures and human subject
safeguards that must be followed in the
clinical tests of investigational new
drugs.
The IND information collection
requirements provide the means by
which FDA can monitor the clinical
investigation of the safety and
effectiveness of unapproved new drugs
and biological products, including the
following: (1) Monitor the safety of
ongoing clinical investigations; (2)
determine whether the clinical testing of
a drug should be authorized; (3) ensure
production of reliable data on the
metabolism and pharmacological action
of the drug in humans; (4) obtain timely
information on adverse reactions to the
drug; (5) obtain information on side
effects associated with increasing doses;
(6) obtain information on the drug’s
effectiveness; (7) ensure the design of
well-controlled, scientifically valid
studies; and (8) obtain other information
pertinent to determining whether
clinical testing should be continued,
and information related to the
protection of human subjects. Without
the information provided by industry as
required under the IND regulations,
FDA cannot authorize or monitor the
clinical investigations which must be
conducted prior to authorizing the sale
and general use of new drugs. These
reports enable FDA to monitor a study’s
E:\FR\FM\03MRN1.SGM
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]]>Agencies
[Federal Register Volume 80, Number 41 (Tuesday, March 3, 2015)]
[Notices]
[Pages 11444-11449]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2015-04381]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2005-N-0161]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Current Good
Manufacturing Practices and Related Regulations for Blood and Blood
Components; and Requirements for Donor Testing, Donor Notification, and
``Lookback''
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by April
2, 2015.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
FAX: 202-395-7285, or emailed to oira_submission@omb.eop.gov. All
comments should be identified with the OMB control number 0910-0116.
Also include the FDA docket number found in brackets in the heading of
this document.
FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations,
Food and Drug Administration, 8455 Colesville Rd., COLE-14526, Silver
Spring, MD 20993-0002, PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Current Good Manufacturing Practices and Related Regulations for Blood
and Blood Components; and Requirements for Donor Testing, Donor
Notification, and ``Lookback''--(OMB Control Number 0910-0116)--
Extension
All blood and blood components introduced or delivered for
introduction into interstate commerce are subject to section 351(a) of
the Public Health Service Act (PHS Act) (42 U.S.C. 262(a)). Section
351(a) requires that manufacturers of biological products, which
include blood and blood components intended for further
[[Page 11445]]
manufacture into injectable products, have a license, issued upon a
demonstration that the product is safe, pure, and potent and that the
manufacturing establishment meets all applicable standards, including
those prescribed in the FDA regulations designed to ensure the
continued safety, purity, and potency of the product. In addition,
under section 361 of the PHS Act (42 U.S.C. 264), by delegation from
the Secretary of Health and Human Services, FDA may make and enforce
regulations necessary to prevent the introduction, transmission, or
spread of communicable diseases from foreign countries into the States
or possessions, or from one State or possession into any other State or
possession.
Section 351(j) of the PHS Act states that the Federal Food, Drug,
and Cosmetic (FD&C) Act also applies to biological products. Blood and
blood components for transfusion or for further manufacture into
injectable products are drugs, as that term is defined in section
201(g)(1) of the FD&C Act (21 U.S.C. 321(g)(1)). Because blood and
blood components are drugs under the FD&C Act, blood and plasma
establishments must comply with the substantive provisions and related
regulatory scheme of the FD&C Act. For example, under section 501 of
the FD&C Act (21 U.S.C. 351(a)), drugs are deemed ``adulterated'' if
the methods used in their manufacturing, processing, packing, or
holding do not conform to current good manufacturing practice (CGMP)
and related regulations.
The CGMP regulations for blood and blood components (21 CFR part
606) and related regulations implement FDA's statutory authority to
ensure the safety, purity, and potency of blood and blood components.
The public health objective in testing human blood donors for evidence
of infection due to communicable disease agents and in notifying donors
is to prevent the transmission of communicable disease. For example,
the ``lookback'' requirements are intended to help ensure the continued
safety of the blood supply by providing necessary information to users
of blood and blood components and appropriate notification of
recipients of transfusion who are at increased risk for transmitting
human immunodeficiency virus (HIV) or hepatitis C virus (HCV)
infection.
The information collection requirements in the CGMP, donor testing,
donor notification, and ``lookback'' regulations provide FDA with the
necessary information to perform its duty to ensure the safety, purity,
and potency of blood and blood components. These requirements establish
accountability and traceability in the processing and handling of blood
and blood components and enable FDA to perform meaningful inspections.
The recordkeeping requirements serve preventive and remedial
purposes. The third-party disclosure requirements identify the various
blood and blood components and important properties of the product,
demonstrate that the CGMP requirements have been met, and facilitate
the tracing of a product back to its original source. The reporting
requirements inform FDA of certain information that may require
immediate corrective action.
Under the reporting requirements, Sec. 606.170(b), in brief,
requires that facilities notify FDA's Center for Biologics Evaluation
and Research (CBER), as soon as possible after confirming a
complication of blood collection or transfusion to be fatal. The
collecting facility is to report donor fatalities, and the
compatibility testing facility is to report recipient fatalities. The
regulation also requires the reporting facility to submit a written
report of the investigation within 7 days after the fatality. In fiscal
year 2013, FDA received 72 of these reports.
Section 610.40(g)(2) (21 CFR 610.40(g)(2)) requires an
establishment to obtain written approval from FDA to ship human blood
or blood components for further manufacturing use prior to completion
of testing for evidence of infection due to certain communicable
disease agents.
Section 610.40(h)(2)(ii)(A), in brief, requires an establishment to
obtain written approval from FDA to use or ship human blood or blood
components found to be reactive by a screening test for evidence of
certain communicable disease agent(s) or collected from a donor with a
record of a reactive screening test.
Under the third-party disclosure requirements, Sec.
610.40(c)(1)(ii), in brief, requires that each donation dedicated to a
single identified recipient be labeled as required under Sec. 606.121
and with a label containing the name and identifying information of the
recipient. The information collection requirements under Sec. 606.121
are part of usual and customary business practice.
Sections 610.40(h)(2)(ii)(C) and (h)(2)(ii)(D), in brief, require
an establishment to label certain reactive human blood and blood
components with the appropriate screening test results, and, if they
are intended for further manufacturing use into injectable products, to
include a statement on the label indicating the exempted use
specifically approved by FDA. Also, Sec. 610.40(h)(2)(vi) requires
each donation of human blood or blood components, excluding Source
Plasma, that tests reactive by a screening test for syphilis and is
determined to be a biological false positive to be labeled with both
test results.
Section 610.42(a) requires a warning statement ``indicating that
the product was manufactured from a donation found to be reactive by a
screening test for evidence of infection due to the identified
communicable disease agent(s)'' in the labeling for medical devices
containing human blood or a blood component found to be reactive by a
screening test for evidence of infection due to a communicable disease
agent(s) or syphilis.
In brief, Sec. Sec. 610.46 and 610.47 require blood collecting
establishments to establish, maintain, and follow an appropriate system
for performing HIV and HCV prospective ``lookback'' when: (1) A donor
tests reactive for evidence of HIV or HCV infection or (2) the
collecting establishment becomes aware of other reliable test results
or information indicating evidence of HIV or HCV infection (prospective
``lookback'') (see Sec. Sec. 610.46(a)(1) and 610.47(a)(1)). The
requirement for ``an appropriate system'' requires the collecting
establishment to design standard operating procedures (SOPs) to
identify and quarantine all blood and blood components previously
collected from a donor who later tests reactive for evidence of HIV or
HCV infection, or when the collecting establishment is made aware of
other reliable test results or information indicating evidence of HIV
or HCV infection. Within 3 calendar days of the donor testing reactive
by an HIV or HCV screening test or the collecting establishment
becoming aware of other reliable test results or information, the
collecting establishment must, among other things, notify consignees to
quarantine all identified previously collected in-date blood and blood
components (Sec. Sec. 610.46(a)(1)(ii)(B) and 610.47(a)(1)(ii)(B))
and, within 45 days, notify the consignees of supplemental test
results, or the results of a reactive screening test if there is no
available supplemental test that is approved for such use by FDA
(Sec. Sec. 610.46(a)(3) and 610.47(a)(3)).
Consignees also must establish, maintain, and follow an appropriate
system for performing HIV and HCV ``lookback'' when notified by the
collecting establishment that they have received blood and blood
components previously collected from donors who later tested reactive
for evidence of HIV or HCV infection, or when the collecting
[[Page 11446]]
establishment is made aware of other reliable test results or
information indicating evidence of HIV or HCV infection in a donor
(Sec. Sec. 610.46(b) and 610.47(b)). This provision for a system
requires the consignee to establish SOPs for, among other things,
notifying transfusion recipients of blood and blood components, or the
recipient's physician of record or legal representative, when such
action is indicated by the results of the supplemental (additional,
more specific) tests or a reactive screening test if there is no
available supplemental test that is approved for such use by FDA, or if
under an investigational new drug application (IND) or an
investigational device exemption (IDE), is exempted for such use by
FDA. The consignee must make reasonable attempts to perform the
notification within 12 weeks of receipt of the supplemental test result
or receipt of a reactive screening test result when there is no
available supplemental test that is approved for such use by FDA, or if
under an IND or IDE, is exempted for such use by FDA (Sec. Sec.
610.46(b)(3) and 610.47(b)(3)).
Section 630.6(a) (21 CFR 630.6(a)) requires an establishment to
make reasonable attempts to notify any donor who has been deferred as
required by Sec. 610.41, or who has been determined not to be eligible
as a donor. Section 630.6(d)(1) requires an establishment to provide
certain information to the referring physician of an autologous donor
who is deferred based on the results of tests as described in Sec.
610.41.
Under the recordkeeping requirements, Sec. 606.100(b), in brief,
requires that written SOPs be maintained for all steps to be followed
in the collection, processing, compatibility testing, storage, and
distribution of blood and blood components used for transfusion and
further manufacturing purposes. Section 606.100(c) requires the review
of all records pertinent to the lot or unit of blood prior to release
or distribution. Any unexplained discrepancy or the failure of a lot or
unit of final product to meet any of its specifications must be
thoroughly investigated, and the investigation, including conclusions
and followup, must be recorded.
In brief, Sec. 606.110(a) provides that the use of
plateletpheresis and leukapheresis procedures to obtain a product for a
specific recipient may be at variance with the additional standards for
that specific product if, among other things, the physician certifies
in writing that the donor's health permits plateletpheresis or
leukapheresis. Section 606.110(b) requires establishments to request
prior approval from CBER for plasmapheresis of donors who do not meet
donor requirements. The information collection requirements for Sec.
606.110(b) are approved under OMB control number 0910-0338 and,
therefore, are not reflected in tables 1 and 2.
Section 606.151(e) requires that SOPs for compatibility testing
include procedures to expedite transfusion in life-threatening
emergencies; records of all such incidents must be maintained,
including complete documentation justifying the emergency action, which
must be signed by a physician.
So that each significant step in the collection, processing,
compatibility testing, storage, and distribution of each unit of blood
and blood components can be clearly traced, Sec. 606.160 requires that
legible and indelible contemporaneous records of each such step be made
and maintained for no less than 10 years. Section 606.160(b)(1)(viii)
requires records of the quarantine, notification, testing and
disposition performed under the HIV and HCV ``lookback'' provisions.
Furthermore, Sec. 606.160(b)(1)(ix) requires a blood collection
establishment to maintain records of notification of donors deferred or
determined not to be eligible for donation, including appropriate
followup. Section 606.160(b)(1)(xi) requires an establishment to
maintain records of notification of the referring physician of a
deferred autologous donor, including appropriate followup.
Section 606.165, in brief, requires that distribution and receipt
records be maintained to facilitate recalls, if necessary.
Section 606.170(a) requires records to be maintained of any reports
of complaints of adverse reactions arising as a result of blood
collection or transfusion. Each such report must be thoroughly
investigated, and a written report, including conclusions and followup,
must be prepared and maintained. Section 606.170(a) also requires that
when an investigation concludes that the product caused the transfusion
reaction, copies of all such written reports must be forwarded to and
maintained by the manufacturer or collecting facility.
Section 610.40(g)(1) requires an establishment to appropriately
document a medical emergency for the release of human blood or blood
components prior to completion of required testing.
In addition to the CGMP regulations in part 606, there are
regulations in 21 CFR part 640 that require additional standards for
certain blood and blood components as follows: Sections 640.3(a)(1),
(a)(2), and (f); 640.4(a)(1) and (a)(2); 640.25(b)(4) and (c)(1);
640.27(b); 640.31(b); 640.33(b); 640.51(b); 640.53(b) and (c);
640.56(b) and (d); 640.61; 640.63(b)(3), (e)(1), and (e)(3);
640.65(b)(2); 640.66; 640.71(b)(1); 640.72; 640.73; and 640.76(a) and
(b). The information collection requirements and estimated burdens for
these regulations are included in the part 606 burden estimates, as
described in tables 1 and 2.
Respondents to this collection of information are licensed and
unlicensed blood establishments that collect blood and blood
components, including Source Plasma and Source Leukocytes, inspected by
FDA, and other transfusion services inspected by Centers for Medicare
and Medicaid Services (CMS). Based on information received from CBER's
database systems, there are approximately 416 licensed Source Plasma
establishments with multiple locations and approximately 1,265 licensed
blood collection establishments, for an estimated total of 1,681
licensed blood collection establishments. Also, there are an estimated
total of 680 unlicensed, registered blood collection establishments for
an approximate total of 2,361 collection establishments (416 + 1,265 +
680 = 2,361 establishments). Of these establishments, approximately 990
perform plateletpheresis and leukapheresis. These establishments
annually collect approximately 40 million units of Whole Blood and
blood components, including Source Plasma and Source Leukocytes, and
are required to follow FDA ``lookback'' procedures. In addition, there
are another 4,961 establishments that fall under the Clinical
Laboratory Improvement Amendments of 1988 (CLIA) (Pub. L. 100-578)
(formerly referred to as facilities approved for Medicare
reimbursement) that transfuse blood and blood components.
The following reporting and recordkeeping estimates are based on
information provided by industry, CMS, and FDA experience. Based on
information received from industry, we estimate that there are
approximately 25 million donations of Source Plasma from approximately
2 million donors and approximately 15 million donations of Whole Blood,
including approximately 225,000 (approximately 1.5 percent of 15
million) autologous donations, from approximately 10.9 million donors.
Assuming each autologous donor makes an average of 2 donations, FDA
estimates that there are approximately 112,500 autologous donors.
FDA estimates that approximately 5 percent (3,600) of the 72,000
donations
[[Page 11447]]
that are donated specifically for the use of an identified recipient
would be tested under the dedicated donors' testing provisions in Sec.
610.40(c)(1)(ii).
Under Sec. Sec. 610.40(g)(2) and (h)(2)(ii)(A), Source Leukocytes,
a licensed product that is used in the manufacture of interferon, which
requires rapid preparation from blood, is currently shipped prior to
completion of testing for evidence of certain communicable disease
agents. Shipments of Source Leukocytes are preapproved under a
biologics license application (BLA) and each shipment does not have to
be reported to the Agency. Based on information from CBER's database
system, FDA receives less than one application per year from
manufacturers of Source Leukocytes. However, for calculation purposes,
we are estimating one application annually.
Under Sec. Sec. 610.40(h)(2)(ii)(C) and (h)(2)(ii)(D), FDA
estimates that each manufacturer would ship an estimated 1 unit of
human blood or blood components per month (12 per year) that would
require two labels; one as reactive for the appropriate screening test
under Sec. 610.40(h)(2)(ii)(C), and the other stating the exempted use
specifically approved by FDA under Sec. 610.40(h)(2)(ii)(D). According
to CBER's database system, there are approximately 40 licensed
manufacturers that ship known reactive human blood or blood components.
Based on information we received from industry, we estimate that
approximately 18,000 donations: (1) Annually test reactive by a
screening test for syphilis; (2) are determined to be biological false
positives by additional testing; and (3) are labeled accordingly (Sec.
610.40(h)(2)(vi)).
Human blood or a blood component with a reactive screening test, as
a component of a medical device, is an integral part of the medical
device, e.g., a positive control for an in vitro diagnostic testing
kit. It is usual and customary business practice for manufacturers to
include on the container label a warning statement that identifies the
communicable disease agent. In addition, on the rare occasion when a
human blood or blood component with a reactive screening test is the
only component available for a medical device that does not require a
reactive component, then a warning statement must be affixed to the
medical device. To account for this rare occasion under Sec.
610.42(a), we estimate that the warning statement would be necessary no
more than once a year.
FDA estimates that approximately 3,500 repeat donors will test
reactive on a screening test for HIV. We also estimate that an average
of three components was made from each donation. Under Sec. Sec.
610.46(a)(1)(ii)(B) and (a)(3), this estimate results in 10,500 (3,500
x 3) notifications of the HIV screening test results to consignees by
collecting establishments for the purpose of quarantining affected
blood and blood components, and another 10,500 (3,500 x 3)
notifications to consignees of subsequent test results.
We estimate that Sec. 610.46(b)(3) will require 4,961 consignees
to notify transfusion recipients, their legal representatives, or
physicians of record an average of 0.35 times per year resulting in a
total number of 1,755 (585 confirmed positive repeat donors x 3)
notifications. Also under Sec. 610.46(b)(3), we estimate and include
the time to gather test results and records for each recipient and to
accommodate multiple attempts to contact the recipient.
Furthermore, we estimate that approximately 7,800 repeat donors per
year would test reactive for antibody to HCV. Under Sec. Sec.
610.47(a)(1)(ii)(B) and 610.47(a)(3), collecting establishments would
notify the consignee 2 times for each of the 23,400 (7,800 x 3
components) components prepared from these donations, once for
quarantine purposes and again with additional HCV test results for a
total of 46,800 notifications as an annual ongoing burden. Under Sec.
610.47(b)(3), we estimate that approximately 4,961 consignees would
notify approximately 2,050 recipients or their physicians of record
annually.
Based on industry estimates, approximately 13 percent of
approximately 10 million potential donors (1.3 million donors) who come
to donate annually are determined not to be eligible for donation prior
to collection because of failure to satisfy eligibility criteria. It is
the usual and customary business practice of approximately 1,945 (1,265
+ 680) blood collecting establishments to notify onsite and to explain
why the donor is determined not to be suitable for donating. Based on
such available information, we estimate that two-thirds (1,297) of the
1,945 blood collecting establishments provided onsite additional
information and counseling to a donor determined not to be eligible for
donation as usual and customary business practice. Consequently, we
estimate that only one-third, or 648, approximately, blood collecting
establishments would need to provide, under Sec. 630.6(a), additional
information and onsite counseling to the estimated 433,333 (one-third
of approximately 1.3 million) ineligible donors.
It is estimated that another 4.5 percent of 10 million potential
donors (450,000 donors) are deferred annually based on test results. We
estimate that approximately 95 percent of the establishments that
collect 99 percent of the blood and blood components notify donors who
have reactive test results for HIV, Hepatitis B Virus, HCV, Human T-
Lymphotropic Virus, and syphilis as usual and customary business
practice. Consequently, 5 percent of the 1,681 establishments (84)
collecting 1 percent (4,500) of the deferred donors (450,000) would
notify donors under Sec. 630.6(a).
As part of usual and customary business practice, collecting
establishments notify an autologous donor's referring physician of
reactive test results obtained during the donation process required
under Sec. 630.6(d)(1). However, we estimate that approximately 5
percent of the 1,265 blood collection establishments (63) may not
notify the referring physicians of the estimated 2 percent of 112,500
autologous donors with the initial reactive test results (2,250) as
their usual and customary business practice.
The recordkeeping chart reflects the estimate that approximately 95
percent of the recordkeepers, which collect 99 percent of the blood
supply, have developed SOPs as part of their customary and usual
business practice. Establishments may minimize burdens associated with
CGMP and related regulations by using model standards developed by
industries' accreditation organizations. These accreditation
organizations represent almost all registered blood establishments.
Under Sec. 606.160(b)(1)(ix), we estimate the total annual records
based on the approximately 1.3 million donors determined not to be
eligible to donate and each of the estimated 1.75 million (1.3 million
+ 450,000) donors deferred based on reactive test results for evidence
of infection because of communicable disease agents. Under Sec.
606.160(b)(1)(xi), only the 1,945 registered blood establishments
collect autologous donations and, therefore, are required to notify
referring physicians. We estimate that 4.5 percent of the 112,500
autologous donors (5,063) will be deferred under Sec. 610.41, which in
turn will lead to the notification of their referring physicians.
FDA has concluded that the use of untested or incompletely tested
but appropriately documented human blood or blood components in rare
medical emergencies should not be prohibited. We estimate the
recordkeeping under Sec. 610.40(g)(1) to be minimal with one or fewer
occurrences per year. The reporting of test results to the consignee
[[Page 11448]]
in Sec. 610.40(g) is part of the usual and customary business practice
or procedure to finish the testing and provide the results to the
manufacturer responsible for labeling the blood products.
The average burden per response (hours) and average burden per
recordkeeping (hours) are based on estimates received from industry or
FDA experience with similar reporting or recordkeeping requirements.
In the Federal Register of October 20, 2014 (79 FR 62629), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. FDA received five comments; however, the
comments were not responsive to the comment request on the four
specified aspects of the collection of information and did not provide
any data or explanation that would support a change regarding the
information collection estimates.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
606.170(b) \2\.................. 72 1 72 20 1,440
610.40(g)(2).................... 1 1 1 1 1
610.40(h)(2)(ii)(A)............. 1 1 1 1 1
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,442
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ The reporting requirement in Sec. 640.73, which addresses the reporting of fatal donor reactions, is
included in the estimate for Sec. 606.170(b).
Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of records per Total annual Average burden Total hours
recordkeepers recordkeeper records per recordkeeping
----------------------------------------------------------------------------------------------------------------
606.100(b) \2\................ \5\ 366 1 366 24............... 8,784
606.100(c).................... \5\ 366 10 3,660 1................ 3,660
606.110(a) \3\................ \6\ 50 1 50 0.5 (30 minutes). 25
606.151(e).................... \5\ 366 12 4,392 0.08 (5 minutes). 351
606.160 \4\................... \5\ 366 1,046.45 383,000 0.75 (45 minutes) 287,250
606.160(b)(1)(viii)........... 1,945 10.80 21,000 0.17 (10 minutes) 3,570
HIV consignee notification.... 4,961 4.23 21,000 0.17 (10 minutes) 3,570
606.160(b)(1)(viii)........... 1,945 24.06 46,800 0.17 (10 minutes) 7,956
HCV consignee notification.... 4,961 9.43 46,800 0.17 (10 minutes) 7,956
HIV recipient notification.... 4,961 0.35 1,755 0.17 (10 minutes) 298
HCV recipient notification.... 4,961 0.41 2,050 0.17 (10 minutes) 349
606.160(b)(1)(ix)............. 2,361 741.21 1,750,000 0.05 (3 minutes). 87,500
606.160(b)(1)(xi)............. 1,945 2.6 5,063 0.05 (3 minutes). 253
606.165....................... \5\ 366 1,046.45 383,000 0.08 (5 minutes). 30,640
606.170(a).................... \5\ 366 12 4,392 1................ 4,392
610.40(g)(1).................. 2,361 1 2,361 0.5 (30 minutes). 1,180
---------------------------------------------------------------------------------
Total..................... .............. ............. .............. ................. 447,734
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ The recordkeeping requirements in Sec. Sec. 640.3(a)(1), 640.4(a)(1), and 640.66, which address the
maintenance of SOPs, are included in the estimate for Sec. 606.100(b).
\3\ The recordkeeping requirements in Sec. 640.27(b), which address the maintenance of donor health records
for the plateletpheresis, are included in the estimate for Sec. 606.110(a).
\4\ The recordkeeping requirements in Sec. Sec. 640.3(a)(2) and (f); 640.4(a)(2); 640.25(b)(4) and (c)(1);
640.31(b); 640.33(b); 640.51(b); 640.53(b) and (c); 640.56(b) and (d); 640.61; 640.63(b)(3), (e)(1), and
(e)(3); 640.65(b)(2); 640.71(b)(1); 640.72; and 640.76(a) and (b), which address the maintenance of various
records, are included in the estimate for Sec. 606.160.
\5\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered
blood establishments (0.05 x 4,961 + 2,361 = 366).
\6\ Five percent of plateletpheresis and leukapheresis establishments (0.05 x 990 = 50).
Table 3--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
606.170(a).................... \2\ 366 1.2 439 0.5 (30 minutes). 220
610.40(c)(1)(ii).............. 2,361 1.52 3,600 0.08 (5 minutes). 288
610.40(h)(2)(ii)(C) and 40 12 480 0.2 (12 minutes). 96
(h)(2)(ii)(D).
610.40(h)(2)(vi).............. 2,361 7.62 18,000 0.08 (5 minutes). 1,440
610.42(a)..................... 1 1 1 1................ 1
610.46(a)(1)(ii)(B)........... 1,945 5.40 10,500 0.17 (10 minutes) 1,785
610.46(a)(3).................. 1,945 5.40 10,500 0.17 (10 minutes) 1,785
610.46(b)(3).................. 4,961 0.35 1,755 1................ 1,755
610.47(a)(1)(ii)(B)........... 1,945 12.03 23,400 0.17 (10 minutes) 3,978
[[Page 11449]]
610.47(a)(3).................. 1,945 12.03 23,400 0.17 (10 minutes) 3,978
610.47(b)(3).................. 4,961 0.41 2,050 1................ 2,050
630.6(a) \3\.................. 648 668.72 433,333 0.08 (5 minutes). 34,667
630.6(a) \4\.................. 84 53.57 4,500 1.5 (90 minutes). 6,750
630.6(d)(1)................... 63 35.71 2,250 1................ 2,250
---------------------------------------------------------------------------------
Total..................... .............. ............. .............. ................. 61,043
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered
blood establishments (0.05 x 4,961 + 2,361 = 366).
\3\ Notification of donors determined not to be eligible for donation based on failure to satisfy eligibility
criteria.
\4\ Notification of donors deferred based on reactive test results for evidence of infection due to communicable
disease agents.
Dated: February 25, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-04381 Filed 3-2-15; 8:45 am]
BILLING CODE 4164-01-P
