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”, 79692-79697 [2011-32778]
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Federal Register / Vol. 76, No. 246 / Thursday, December 22, 2011 / Notices
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1—Continued
21 CFR Section
607.21, 607.25, 607.30(a),
607.31, and 607.40.
Total
hours
180
0.25
(15 min.)
45
.....................................................
........................
........................
....................
....................
1,389
are no capital costs or operating and maintenance costs associated with this collection of information.
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:
BILLING CODE 4160–01–P
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
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–N–0511]
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’’
Food and Drug Administration,
HHS.
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 January 23,
2012.
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.
SUMMARY:
jlentini on DSK4TPTVN1PROD with NOTICES
Average
burden per
response
1
[FR Doc. 2011–32777 Filed 12–21–11; 8:45 am]
ACTION:
Total annual
responses
180
Dated: December 19, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
AGENCY:
Number of
responses per
respondent
Product listing update .................
Total .....................................
1 There
Number of
respondents
FDA Form 2830
Ila
S. Mizrachi, Food and Drug
Administration, 1350 Piccard Dr., PI50–
400B, Rockville, MD 20850, (301) 796–
7726, Ila.Mizrachi@fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
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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).
Section 351(a) of the PHS Act requires
that manufacturers of biological
products, which include blood and
blood components intended for further
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 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 Federal, Food, Drug, and
Cosmetics Act (21 U.S.C. 321(g)(1)).
Because blood and blood components
are drugs under the Federal, Food, Drug,
and Cosmetics Act, blood and plasma
establishments must comply with the
substantive provisions and related
regulatory scheme of the act. For
example, under section 501 of the
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Fmt 4703
Sfmt 4703
Federal, Food, Drug, and Cosmetic 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 in part 606 (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
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
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(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 2010,
FDA received 76 of these reports.
Section 610.40(c)(1)(ii) in part 610 (21
CFR part 610), 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.
Section 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. Furthermore,
§§ 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. Finally, § 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
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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
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
(standard operating procedures) 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
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79693
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 leukaphesis
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 § 606.110(b) are approved under
OMB control number 0910–0338 and,
therefore, are not reflected in tables 1
and 2 of this document.
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
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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 (21 CFR 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. 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 part
640 (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 of this document.
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 31 licensed Source
Plasma establishments with multiple
locations and approximately 1,675
registered blood collection
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establishments, for an estimated total of
1,706 establishments. Of these
establishments, approximately 1,032
perform plateletpheresis and
leukopheresis. These establishments
annually collect approximately 38.3
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 4,059 establishments that fall
under the Clinical Laboratory
Improvement Amendments of 1988
(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 21
million donations of Source Plasma
from approximately 2 million donors
and approximately 17.3 million
donations of Whole Blood, including
approximately 261,000 (approximately
1.5 percent of 17.3 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 130,500 autologous
donors.
FDA estimates that approximately 5
percent (3,600 of the 72,000 donations
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
pre-approved under a biologics license
application 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
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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
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 an average of 10 minutes
per notification of consignees.
We estimate that § 610.46(b)(3) will
require 4,059 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. Under § 610.46(b)(3), we
also estimate 1 hour to accommodate
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
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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 4,059
consignees would notify approximately
2,050 recipients or their physicians of
record annually. Finally, we estimate
1 hour to complete notification.
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 1,675 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 (1,117) of the 1,675
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 558, approximately, blood
collecting establishments would need to
provide, under § 630.6(a), additional
information and onsite counseling to the
estimated 433,000 (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 (HBV), HCV,
Human T-Lymphotropic Virus (HTLV),
and syphilis as usual and customary
business practice. Consequently, 5
percent of the 1,706 establishments (85)
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 1,675
blood collection establishments (84)
may not notify the referring physicians
of the estimated 2 percent of 130,500
autologous donors with the initial
reactive test results (2,610) 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 1,675
registered blood establishments collect
autologous donations and, therefore, are
required to notify referring physicians.
We estimate that 4.5 percent of the
130,500 autologous donors (5,872) 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
in § 610.40(g) does not create a new
burden for respondents because it is 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 hours per response and hours per
record are based on estimates received
from industry or FDA experience with
similar recordkeeping or reporting
requirements.
In the Federal Register of July 28,
2011 (76 FR 45262), FDA published a
60-day notice requesting public
comment on the proposed collection of
information. No comments were
received.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN
Number of
respondents
21 CFR section
Number of
responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
606.170(b) 1 ..........................................................................
610.40(g)(2) .........................................................................
610.40(h)(2)(ii)(A) .................................................................
76
1
1
1
1
1
76
1
1
20
1
1
1,520
1
1
Total ..............................................................................
........................
........................
........................
........................
1,522
1 The
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
Number of
recordkeepers
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21 CFR section
606.100(b) 1 ..........................................................................
606.100(c) ............................................................................
606.110(a) 2 ..........................................................................
4 288
606.151(e) ............................................................................
Number of
records per
recordkeeper
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Frm 00050
Total annual
records
5 52
1.20
10
1
346
2,880
52
4 288
12
3,456
4 288
Fmt 4703
Sfmt 4703
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Average
burden per
recordkeeping
24
1
0.50
(30 min.)
0.08
(5 min.)
Total hours
6,912
2,880
26
276
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TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN—Continued
Number of
recordkeepers
21 CFR section
Number of
records per
recordkeeper
Total annual
records
606.160 3 ..............................................................................
4 288
1,329.86
383,000
606.160(b)(1)(viii) .................................................................
HIV consignee notification ...................................................
........................
1,675
........................
12.54
........................
21,000
4,059
5.17
21,000
1,675
27.94
46,800
4,059
11.53
46,800
HIV recipient notification ......................................................
4,059
0.43
1,755
HCV recipient notification ....................................................
4,059
0.51
2,050
606.160(b)(1)(ix) ..................................................................
1,706
1,025.79
1,750,000
606.160(b)(1)(xi) ..................................................................
1,675
3.51
5,872
606.165 ................................................................................
5 288
1,329.86
383,000
606.170(a) ............................................................................
610.40(g)(1) .........................................................................
5 288
1,706
12
1
3,456
1,706
Total ..............................................................................
........................
........................
........................
HCV consignee notification ..................................................
Average
burden per
recordkeeping
0.75
(45 min.)
........................
.17
(10 min.)
.17
(10 min.)
.17
(10 min.)
.17
(10 min.)
.17
(10 min.)
.17
(10 min.)
0.05
(3 min.)
0.05
(3 min.)
0.08
(5 min.)
1
0.50
(30 min.)
........................
Total hours
287,250
........................
3,570
3,570
7,956
7,956
298
349
87,500
294
30,640
3,456
853
443,786
1 The
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).
2 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).
3 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.
4 Five percent of establishments that fall under the Clinical Laboratory Improvement Amendments of 1988 that transfuse blood and components and FDA-registered blood establishments (0.05 × 4,059 + 1,706).
5 Five percent of plateletpheresis and leukopheresis establishments (0.05 × 1,032).
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN
Number of
respondents
21 CFR section
Number of
disclosures
per
respondent
Total annual
disclosures
1 288
1.20
346
610.40(c)(1)(ii) ......................................................................
1,706
2.11
3,600
610.40(h)(2)(ii)(C) and (h)(2)(ii)(D) ......................................
40
12
480
610.40(h)(2)(vi) ....................................................................
1,706
10.55
18,000
610.42(a) ..............................................................................
610.46(a)(1)(ii)(B) .................................................................
1
1,675
1
6.27
1
10,500
610.46(a)(3) .........................................................................
1,675
6.27
10,500
610.46(b)(3) .........................................................................
610.47(a)(1)(ii)(B) .................................................................
4,059
1,675
0.43
13.97
1,755
23,400
610.47(a)(3) .........................................................................
jlentini on DSK4TPTVN1PROD with NOTICES
606.170(a) ............................................................................
1,675
13.97
23,400
610.47(b)(3) .........................................................................
630.6(a) 2 ..............................................................................
4,059
558
0.51
755.98
2,050
433,000
630.6(a) 3 ..............................................................................
85
52.94
4,500
630.6(d)(1) ...........................................................................
84
31.07
2,610
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E:\FR\FM\22DEN1.SGM
22DEN1
Average
burden per
disclosure
0.50
(30 min.)
0.08
(5 min.)
0.20
(12 min.)
0.08
(5 min.)
1
0.17
(10 min.)
0.17
(10 min.)
1
0.17
(10 min.)
0.17
(10 min.)
1
0.08
(5 min.)
1.50
(90 min.)
1
Total hours
173
288
96
1,440
1
1,785
1,785
1,755
3,978
3,978
2,050
34,640
6,750
2,610
Federal Register / Vol. 76, No. 246 / Thursday, December 22, 2011 / Notices
79697
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN—Continued
Number of
respondents
21 CFR section
Total ..............................................................................
Number of
disclosures
per
respondent
Total annual
disclosures
Average
burden per
disclosure
........................
........................
........................
........................
Total hours
61,329
1 Five
percent of establishments that fall under the Clinical Laboratory Improvement Amendments of 1988 that transfuse blood and components and FDA-registered blood establishments (0.05 × 4,059 + 1,706).
2 Notification of donors determined not to be eligible for donation based on failure to satisfy eligibility criteria.
3 Notification of donors deferred based on reactive test results for evidence of infection due to communicable disease agents.
Dated: December 16, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011–32778 Filed 12–21–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA–1977–N–0019 (formerly
1977N–0230), FDA–1977–N–0014 (formerly
977N–0231), FDA–1977–N–0022 (formerly
1977N–0316), and FDA–1977–N–0224
(formerly 1977N–0317)]
Withdrawal of Notices of Opportunity
for a Hearing; Penicillin and
Tetracycline Used in Animal Feed
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) is
withdrawing two 1977 notices of
opportunity for a hearing (NOOH),
which proposed to withdraw certain
approved uses of penicillin and
tetracyclines intended for use in feeds
for food-producing animals based in
part on microbial food safety concerns.1
(Refs. 1 and 2) FDA is taking this action,
and closing the corresponding dockets,
because: FDA is engaging in other
ongoing regulatory strategies developed
since the publication of the 1977
NOOHs with respect to addressing
microbial food safety issues; FDA would
update the NOOHs to reflect current
data, information, and policies if, in the
future, it decides to move forward with
withdrawal of the approved uses of the
new animal drugs described in the
NOOHs; and FDA would need to
prioritize any withdrawal proceedings
(for example, take into account which
withdrawal(s) would likely have the
jlentini on DSK4TPTVN1PROD with NOTICES
SUMMARY:
1 FDA’s approval to withdraw the approved uses
of the drugs was based on three statutory grounds:
(1) The drugs are not shown to be safe (21 U.S.C.
360b(e)(1)(B)); (2) lack of substantial evidence of
effectiveness (21 U.S.C. 360b(e)(1)(C)); and (3)
failure to submit required reports (21 U.S.C.
360b(e)(2)(A)).
VerDate Mar<15>2010
19:17 Dec 21, 2011
Jkt 226001
most significant impact on the public
health) if, in the future, it decides to
seek withdrawal of the approved uses of
any new animal drug or class of drugs.
FDA is also withdrawing the companion
proposed rules to these NOOHs. (Refs.
3 and 4)
DATES: This notice is effective December
22, 2011.
ADDRESSES: Submit electronic
comments to https://www.regulations.
gov. Submit written comments to the
Division of Dockets Management (HFV–
305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852.
FOR FURTHER INFORMATION CONTACT:
William Flynn, Center for Veterinary
Medicine (HFV–1), Food and Drug
Administration, 7519 Standish Pl.,
Rockville, MD 20855, (240) 276–9000,
email: William.flynn@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Background
Questions regarding the use of
antimicrobial drugs in food-producing
animals have been raised and debated
for many years. (Ref. 5) 2 Following a
report that was issued by the British
government in 1969 on the use of
antibiotics in veterinary medicine and
animal husbandry, known as the
‘‘Swann Report,’’ the Commissioner of
Food and Drugs established a task force
to review the use of antibiotic drugs in
animal feeds. The task force, established
in 1970, included specialists on
infectious diseases and animal science
from FDA, the National Institutes of
Health, the U.S. Department of
2 The term ‘‘antimicrobial’’ refers broadly to drugs
with activity against a variety of microorganisms
including: Bacteria, viruses, fungi, and parasites.
Antimicrobial drugs that have specific activity
against bacteria are referred to as antibacterial or
antibiotic drugs. However, the broader term
‘‘antimicrobial,’’ commonly used in reference to
drugs with activity against bacteria, is used in this
document interchangeably with the terms
antibacterial or antibiotic. Antimicrobial resistance
is the ability of bacteria or other microbes to resist
the effects of a drug. Antimicrobial resistance, as it
relates to bacterial organisms, occurs when bacteria
change in some way that reduces or eliminates the
effectiveness of drugs, chemicals, or other agents
designed to treat bacterial infections. (Ref. 5)
PO 00000
Frm 00052
Fmt 4703
Sfmt 4703
Agriculture, and the Centers for Disease
Control and Prevention, as well as
representatives from universities and
industry. The task force identified three
primary areas of concern (human health
hazard, animal health hazard, and
antibiotic effectiveness) and guidelines
were established to show whether the
use of any antibiotic or antibacterial
agent in animal feed presents a hazard
to human and animal health. (Refs. 1
and 6) The task force also made certain
recommendations concerning
restrictions on the use of antibiotic
drugs in animal feeds at growth
promotion and subtherapeutic levels.
(Ref. 6)
In 1972, FDA published the
conclusions and recommendations of
that task force and proposed to require
sponsors to submit specific data for
antibiotic drugs in animal feeds
intended for subtherapeutic or growth
promotion use when such drugs are also
used in human clinical medicine. (Ref.
6) In 1973, FDA finalized this proposal
in 21 CFR 135.109 (re-codified at 21
CFR 558.15 in 1974).3 (Refs. 7, 8, and 9)
This section provided that FDA would
propose to revoke approved uses in
animal feed of antibiotic and
sulfonamide drugs unless certain data
were submitted which satisfactorily
addressed the outstanding safety and
effectiveness issues.
By 1974, FDA had begun to review
the data submitted by the sponsors of
the antibiotic products and requested
that the National Advisory Food and
Drug Committee (NAFDC) review the
data and make recommendations on the
subtherapeutic uses of penicillin and
tetracyclines. A subcommittee (the
Antibiotics in Animal Feeds
subcommittee) was appointed to work
in conjunction with expert consultants
to address these issues. With respect to
the penicillin-containing drugs, the
subcommittee recommended FDA
immediately withdraw approval of the
subtherapeutic uses of penicillin. The
3 Since that time, portions of 21 CFR 558.15 have
been removed because those portions of the
regulation were determined to be redundant or
obsolete. (See 75 FR 16001, March 31, 2010.)
E:\FR\FM\22DEN1.SGM
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]]>Agencies
[Federal Register Volume 76, Number 246 (Thursday, December 22, 2011)]
[Notices]
[Pages 79692-79697]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-32778]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0511]
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 January
23, 2012.
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: Ila S. Mizrachi, Food and Drug
Administration, 1350 Piccard Dr., PI50-400B, Rockville, MD 20850, (301)
796-7726, Ila.Mizrachi@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). Section 351(a)
of the PHS Act requires that manufacturers of biological products,
which include blood and blood components intended for further
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 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
Federal, Food, Drug, and Cosmetics Act (21 U.S.C. 321(g)(1)). Because
blood and blood components are drugs under the Federal, Food, Drug, and
Cosmetics Act, blood and plasma establishments must comply with the
substantive provisions and related regulatory scheme of the act. For
example, under section 501 of the Federal, Food, Drug, and Cosmetic 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 in part 606 (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 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
[[Page 79693]]
(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 2010, FDA received 76 of these
reports.
Section 610.40(c)(1)(ii) in part 610 (21 CFR part 610), 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.
Section 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. Furthermore, Sec. Sec.
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. Finally, 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
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 (standard operating
procedures) 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 leukaphesis 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 of this document.
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
[[Page 79694]]
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 (21 CFR 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. 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 part 640 (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 of this document.
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 31 licensed Source Plasma
establishments with multiple locations and approximately 1,675
registered blood collection establishments, for an estimated total of
1,706 establishments. Of these establishments, approximately 1,032
perform plateletpheresis and leukopheresis. These establishments
annually collect approximately 38.3 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 4,059 establishments that fall under the Clinical
Laboratory Improvement Amendments of 1988 (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 21 million donations of Source Plasma from approximately
2 million donors and approximately 17.3 million donations of Whole
Blood, including approximately 261,000 (approximately 1.5 percent of
17.3 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 130,500 autologous donors.
FDA estimates that approximately 5 percent (3,600 of the 72,000
donations 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 pre-approved under a
biologics license application 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 an
average of 10 minutes per notification of consignees.
We estimate that Sec. 610.46(b)(3) will require 4,059 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. Under Sec. 610.46(b)(3), we also estimate 1 hour to
accommodate 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
[[Page 79695]]
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 4,059 consignees would
notify approximately 2,050 recipients or their physicians of record
annually. Finally, we estimate 1 hour to complete notification.
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 1,675 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 (1,117) of the 1,675 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 558, approximately, blood collecting establishments
would need to provide, under Sec. 630.6(a), additional information and
onsite counseling to the estimated 433,000 (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 (HBV), HCV, Human
T-Lymphotropic Virus (HTLV), and syphilis as usual and customary
business practice. Consequently, 5 percent of the 1,706 establishments
(85) 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 1,675 blood collection establishments (84) may not
notify the referring physicians of the estimated 2 percent of 130,500
autologous donors with the initial reactive test results (2,610) 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 1,675 registered blood establishments
collect autologous donations and, therefore, are required to notify
referring physicians. We estimate that 4.5 percent of the 130,500
autologous donors (5,872) 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 in
Sec. 610.40(g) does not create a new burden for respondents because it
is 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 hours per response and hours per record are based on estimates
received from industry or FDA experience with similar recordkeeping or
reporting requirements.
In the Federal Register of July 28, 2011 (76 FR 45262), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. No comments were received.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden
----------------------------------------------------------------------------------------------------------------
Number of Average
21 CFR section Number of responses per Total annual burden per Total hours
respondents respondent responses response
----------------------------------------------------------------------------------------------------------------
606.170(b) \1\.................. 76 1 76 20 1,520
610.40(g)(2).................... 1 1 1 1 1
610.40(h)(2)(ii)(A)............. 1 1 1 1 1
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,522
----------------------------------------------------------------------------------------------------------------
\1\ 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
----------------------------------------------------------------------------------------------------------------
Number of Average
21 CFR section Number of records per Total annual burden per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
606.100(b) \1\.................. \4\ 288 1.20 346 24 6,912
606.100(c)...................... \4\ 288 10 2,880 1 2,880
606.110(a) \2\.................. \5\ 52 1 52 0.50 26
(30 min.)
606.151(e)...................... \4\ 288 12 3,456 0.08 276
(5 min.)
[[Page 79696]]
606.160 \3\..................... \4\ 288 1,329.86 383,000 0.75 287,250
(45 min.)
606.160(b)(1)(viii)............. .............. .............. .............. .............. ..............
HIV consignee notification...... 1,675 12.54 21,000 .17 3,570
(10 min.)
4,059 5.17 21,000 .17 3,570
(10 min.)
HCV consignee notification...... 1,675 27.94 46,800 .17 7,956
(10 min.)
4,059 11.53 46,800 .17 7,956
(10 min.)
HIV recipient notification...... 4,059 0.43 1,755 .17 298
(10 min.)
HCV recipient notification...... 4,059 0.51 2,050 .17 349
(10 min.)
606.160(b)(1)(ix)............... 1,706 1,025.79 1,750,000 0.05 87,500
(3 min.)
606.160(b)(1)(xi)............... 1,675 3.51 5,872 0.05 294
(3 min.)
606.165......................... \5\ 288 1,329.86 383,000 0.08 30,640
(5 min.)
606.170(a)...................... \5\ 288 12 3,456 1 3,456
610.40(g)(1).................... 1,706 1 1,706 0.50 853
(30 min.)
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 443,786
----------------------------------------------------------------------------------------------------------------
\1\ 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).
\2\ 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).
\3\ 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.
\4\ Five percent of establishments that fall under the Clinical Laboratory Improvement Amendments of 1988 that
transfuse blood and components and FDA-registered blood establishments (0.05 x 4,059 + 1,706).
\5\ Five percent of plateletpheresis and leukopheresis establishments (0.05 x 1,032).
Table 3--Estimated Annual Third-Party Disclosure Burden
----------------------------------------------------------------------------------------------------------------
Number of
Number of disclosures Total annual Average
21 CFR section respondents per disclosures burden per Total hours
respondent disclosure
----------------------------------------------------------------------------------------------------------------
606.170(a)...................... \1\ 288 1.20 346 0.50 173
(30 min.)
610.40(c)(1)(ii)................ 1,706 2.11 3,600 0.08 288
(5 min.)
610.40(h)(2)(ii)(C) and 40 12 480 0.20 96
(h)(2)(ii)(D).................. (12 min.)
610.40(h)(2)(vi)................ 1,706 10.55 18,000 0.08 1,440
(5 min.)
610.42(a)....................... 1 1 1 1 1
610.46(a)(1)(ii)(B)............. 1,675 6.27 10,500 0.17 1,785
(10 min.)
610.46(a)(3).................... 1,675 6.27 10,500 0.17 1,785
(10 min.)
610.46(b)(3).................... 4,059 0.43 1,755 1 1,755
610.47(a)(1)(ii)(B)............. 1,675 13.97 23,400 0.17 3,978
(10 min.)
610.47(a)(3).................... 1,675 13.97 23,400 0.17 3,978
(10 min.)
610.47(b)(3).................... 4,059 0.51 2,050 1 2,050
630.6(a) \2\.................... 558 755.98 433,000 0.08 34,640
(5 min.)
630.6(a) \3\.................... 85 52.94 4,500 1.50 6,750
(90 min.)
630.6(d)(1)..................... 84 31.07 2,610 1 2,610
-------------------------------------------------------------------------------
[[Page 79697]]
Total....................... .............. .............. .............. .............. 61,329
----------------------------------------------------------------------------------------------------------------
\1\ Five percent of establishments that fall under the Clinical Laboratory Improvement Amendments of 1988 that
transfuse blood and components and FDA-registered blood establishments (0.05 x 4,059 + 1,706).
\2\ Notification of donors determined not to be eligible for donation based on failure to satisfy eligibility
criteria.
\3\ Notification of donors deferred based on reactive test results for evidence of infection due to communicable
disease agents.
Dated: December 16, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-32778 Filed 12-21-11; 8:45 am]
BILLING CODE 4160-01-P
