Agency Information Collection Activities; Proposed Collection; Comment Request; Current Good Manufacturing Practices and Related Regulations for Blood and Blood Components; and Requirements for Donor Testing, Donor Notification, and “Lookback”, 45262-45267 [2011-19040]
Download as PDF
<![CDATA[
45262
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
requests for fast track designation to the
Center for Biologics Evaluation and
Research and the Center for Drug
Evaluation and Research is
approximately 97, and the number of
requests received is approximately 118
annually. FDA estimates that the
number of hours needed to prepare a
request for fast track designation is
approximately 60 hours per request.
Not all requests for fast track
designation may meet the statutory
standard. Of the requests for fast track
designation made per year, the Agency
granted 77 requests from 64
respondents, and for each of these
granted requests a premeeting package
was submitted to the Agency. FDA
estimates that the preparation hours are
approximately 100 hours per
premeeting package.
In the Federal Register of April 13,
2011 (76 FR 20679), 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 1
No. of
respondents
Reporting activity
No. of responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
Designation Requests ..........................................................
Premeeting Packages ..........................................................
97
64
1.22
1.20
118
77
60
100
7,080
7,700
Total ..............................................................................
........................
........................
........................
........................
14,780
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
Dated: July 19, 2011.
David Dorsey,
Acting Deputy Commissioner for Policy,
Planning and Budget.
components; and requirements for
donor testing, donor notification, and
‘‘lookback.’’
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2011–N–0511]
Agency Information Collection
Activities; Proposed Collection;
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 an
opportunity for public comment on the
proposed collection of certain
information by the Agency. Under the
Paperwork Reduction Act of 1995 (the
PRA), Federal Agencies are required to
publish notice in the Federal Register
concerning each proposed collection of
information, including each proposed
extension of an existing collection of
information, and to allow 60 days for
public comment in response to the
notice. This notice solicits comments on
the collection of information
requirements relating to FDA’s
regulation of current good
manufacturing practice (CGMP) and
related regulations for blood and blood
rmajette on DSK89S0YB1PROD with NOTICES
SUMMARY:
VerDate Mar<15>2010
17:52 Jul 27, 2011
Jkt 223001
Submit either electronic or
written comments on the collection of
information by September 26, 2011.
ADDRESSES: Submit electronic
comments on the collection of
information to https://
www.regulations.gov. Submit written
comments on the collection of
information to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
FOR FURTHER INFORMATION CONTACT:
Juanmanuel Vilela, Office of
Information Management, Food and
Drug Administration, 1350 Piccard Dr.,
PI50–400B, Rockville, MD 20850, 301–
796–7651,
Juanmanuel.vilela@fda.hhs.gov.
DATES:
[FR Doc. 2011–19138 Filed 7–27–11; 8:45 am]
Under the
PRA (44 U.S.C. 3501–3520), Federal
Agencies must obtain approval from the
Office of Management and Budget
(OMB) for each collection of
information they conduct or sponsor.
‘‘Collection of information’’ is defined
in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests
or requirements that members of the
public submit reports, keep records, or
provide information to a third party.
Section 3506(c)(2)(A) of the PRA (44
U.S.C. 3506(c)(2)(A)) requires Federal
Agencies to provide a 60-day notice in
the Federal Register concerning each
proposed collection of information,
including each proposed extension of an
existing collection of information,
SUPPLEMENTARY INFORMATION:
PO 00000
Frm 00042
Fmt 4703
Sfmt 4703
before submitting the collection to OMB
for approval. To comply with this
requirement, FDA is publishing notice
of the proposed collection of
information set forth in this document.
With respect to the following
collection of information, FDA invites
comments on these topics: (1) Whether
the proposed collection of information
is necessary for the proper performance
of FDA’s functions, including whether
the information will have practical
utility; (2) the accuracy of FDA’s
estimate of the burden of the proposed
collection of information, including the
validity of the methodology and
assumptions used; (3) ways to enhance
the quality, utility, and clarity of the
information to be collected; and (4)
ways to minimize the burden of the
collection of information on
respondents, including through the use
of automated collection techniques,
when appropriate, and other forms of
information technology.
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
E:\FR\FM\28JYN1.SGM
28JYN1
rmajette on DSK89S0YB1PROD with NOTICES
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
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 (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
CGMP and related regulations.
The CGMP regulations (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
VerDate Mar<15>2010
15:51 Jul 27, 2011
Jkt 223001
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 2010,
FDA received 76 of these reports.
Section 610.40(c)(1)(ii) (21 CFR
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.
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) (21 CFR 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
PO 00000
Frm 00043
Fmt 4703
Sfmt 4703
45263
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 (21 CFR
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
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
E:\FR\FM\28JYN1.SGM
28JYN1
rmajette on DSK89S0YB1PROD with NOTICES
45264
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
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 (21 CFR 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
VerDate Mar<15>2010
15:51 Jul 27, 2011
Jkt 223001
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. 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
PO 00000
Frm 00044
Fmt 4703
Sfmt 4703
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 the 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 § 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
E:\FR\FM\28JYN1.SGM
28JYN1
rmajette on DSK89S0YB1PROD with NOTICES
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
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 2 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
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
VerDate Mar<15>2010
15:51 Jul 27, 2011
Jkt 223001
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
(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 4,059 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, roughly
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)
PO 00000
Frm 00045
Fmt 4703
Sfmt 4703
45265
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.
E:\FR\FM\28JYN1.SGM
28JYN1
45266
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
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
5 288
Total annual
responses
Average burden
per response
Total hours
606.170(a) ................................................................
606.170(b) 2 ..............................................................
610.40(c)(1)(ii) ..........................................................
610.40(g)(2) .............................................................
610.40(h)(2)(ii)(A) .....................................................
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) .....................................................
610.47(a)(3) .............................................................
610.47(b)(3) .............................................................
630.6(a) 3 ..................................................................
630.6(a) 4 ..................................................................
630.6(d)(1) ...............................................................
76
1,706
1
1
40
1,706
1
1,675
1,675
4,059
1,675
1,675
4,059
558
85
84
1.20
1
2.11
1
1
12
10.55
1
6.27
6.27
0.43
13.97
13.97
0.51
775.98
52.94
31.07
346
76
3,600
1
1
480
18,000
1
10,500
10,500
1,755
23,400
23,400
2,050
433,000
4,500
2,610
0.5
20
0.08
1
1
0.2
0.08
1
0.17
0.17
1
0.17
0.17
1
0.08
1.5
1
173
1,520
288
1
1
96
1,440
1
1,785
1,785
1,755
3,978
3,978
2,050
34,640
6,750
2,610
Total ..................................................................
........................
..............................
........................
..............................
62,851
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
2 The reporting requirement in § 640.73, which addresses the reporting of fatal donor reactions, is included in the estimate for § 606.170(b).
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.
5 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).
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
Number of records
per recordkeeper
5 288
5 288
1
10
1
12
1,329.86
288
2,880
52
3,456
383,000
24
1
0.5
0.08
0.75
6,912
2,880
26
276
287,250
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) .............................................................
1,675
4,059
1,675
4,059
4,059
4,059
1,706
1,675
5 288
5 288
1,706
12.54
5.17
27.94
11.53
0.43
0.51
1,025.79
3.51
1,329.86
12
1
21,000
21,000
46,800
46,800
1,755
2,050
1,750,000
5,872
383,000
3,456
1,706
0.17
0.17
0.17
0.17
0.17
0.17
0.05
0.05
0.08
1
0.50
3,570
3,570
7,956
7,956
298
349
87,500
294
30,640
3,456
853
Total ..................................................................
........................
..............................
........................
..............................
443,786
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 ................................
5 288
6 52
5 288
HCV consignee notification ..............................
Total annual
records
Average burden
per recordkeeping
rmajette on DSK89S0YB1PROD with NOTICES
1 There
Total hours
are no capital costs or operating and maintenance costs associated with this collection of information.
2 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).
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 the Clinical Laboratory Improvement Amendments of 1988 that transfuse blood and components and FDA-registered blood establishments (0.05 × 4,059 + 1,706).
6 Five percent of plateletpheresis and leukopheresis establishments (0.05 × 1,032).
VerDate Mar<15>2010
15:51 Jul 27, 2011
Jkt 223001
PO 00000
Frm 00046
Fmt 4703
Sfmt 4703
E:\FR\FM\28JYN1.SGM
28JYN1
Federal Register / Vol. 76, No. 145 / Thursday, July 28, 2011 / Notices
Dated: July 22, 2011.
David Dorsey,
Acting Deputy Commissioner for Policy,
Planning and Budget.
FOR FURTHER INFORMATION CONTACT:
[FR Doc. 2011–19040 Filed 7–27–11; 8:45 am]
BILLING CODE 4160–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2010–N–0318]
Determination That INVERSINE
(Mecamylamine Hydrochloride) Tablet
and Six Other Drug Products Were Not
Withdrawn From Sale for Reasons of
Safety or Effectiveness
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) has determined
that the seven drug products listed in
this document were not withdrawn from
sale for reasons of safety or
effectiveness. This determination means
that FDA will not begin procedures to
withdraw approval of abbreviated new
drug applications (ANDAs) that refer to
these drug products, and it will allow
FDA to continue to approve ANDAs that
refer to the products as long as they
meet relevant legal and regulatory
requirements.
SUMMARY:
Olivia Pritzlaff, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6308,
Silver Spring, MD 20993–0002, 301–
796–3601.
SUPPLEMENTARY INFORMATION: In 1984,
Congress enacted the Drug Price
Competition and Patent Term
Restoration Act of 1984 (Pub. L. 98–417)
(the 1984 amendments), which
authorized the approval of duplicate
versions of drug products approved
under an ANDA procedure. ANDA
applicants must, with certain
exceptions, show that the drug for
which they are seeking approval
contains the same active ingredient in
the same strength and dosage form as
the ‘‘listed drug,’’ which is a version of
the drug that was previously approved.
ANDA applicants do not have to repeat
the extensive clinical testing otherwise
necessary to gain approval of a new
drug application (NDA). The only
clinical data required in an ANDA are
data to show that the drug that is the
subject of the ANDA is bioequivalent to
the listed drug.
The 1984 amendments include what
is now section 505(j)(7) of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C.
355(j)(7)), which requires FDA to
publish a list of all approved drugs.
FDA publishes this list as part of the
‘‘Approved Drug Products With
45267
Therapeutic Equivalence Evaluations,’’
which is generally known as the
‘‘Orange Book.’’ Under FDA regulations,
a drug is withdrawn from the list if the
Agency withdraws or suspends
approval of the drug’s NDA or ANDA
for reasons of safety or effectiveness, or
if FDA determines that the listed drug
was withdrawn from sale for reasons of
safety or effectiveness (21 CFR 314.162).
Under § 314.161(a) (21 CFR
314.161(a)), the Agency must determine
whether a listed drug was withdrawn
from sale for reasons of safety or
effectiveness: (1) Before an ANDA that
refers to that listed drug may be
approved; (2) whenever a listed drug is
voluntarily withdrawn from sale and
ANDAs that refer to the listed drug have
been approved; and (3) when a person
petitions for such a determination under
21 CFR 10.25(a) and 10.30. Section
314.161(d) provides that if FDA
determines that a listed drug was
withdrawn from sale for reasons of
safety or effectiveness, the Agency will
initiate proceedings that could result in
the withdrawal of approval of the
ANDAs that refer to the listed drug.
FDA has become aware that the drug
products listed in the table in this
document are no longer being marketed.
(As requested by the applicant, FDA
withdrew approval of NDA 021039 for
AGENERASE (amprenavir) Oral
Solution in the Federal Register of July
21, 2010 (75 FR 42455).)
Application No.
Drug
Applicant
NDA 010251 ........
INVERSINE (mecamylamine hydrochloride (HCl)) Tablet, 2.5
milligrams (mg).
STELAZINE (trifluoperazine HCl) Injection, Equivalent to
(EQ) 2 mg base/milliliter (mL).
STELAZINE (trifluoperazine HCl) Oral Concentrate, EQ 10
mg base/mL.
SINEQUAN (doxepin HCl) Capsules, EQ 10 mg base, EQ
25 mg base, EQ 50 mg base, EQ 75 mg base, EQ 100
mg base, and EQ 150 mg base.
SINEQUAN (doxepin HCl) Oral Concentrate, EQ 10 mg
base/mL.
VOLTAREN (diclofenac sodium) Delayed-Release Tablet, 75
mg.
AGENERASE (amprenavir) Oral Solution, 15 mg/mL ............
Targacept, Inc., 200 East 1st St., Suite 300, Winston Salem,
NC 27101–4165
GlaxoSmithKline, 5 Moore Dr., P.O. Box 13398, Research
Triangle Park, NC 27709–3398
Do.
NDA 011552 ........
NDA 011552 ........
NDA 016798 ........
NDA 017516 ........
NDA 019201 ........
rmajette on DSK89S0YB1PROD with NOTICES
NDA 021039 ........
FDA has reviewed its records and,
under § 314.161, has determined that
the drug products listed in this
document were not withdrawn from
sale for reasons of safety or
effectiveness. Accordingly, the Agency
will continue to list the drug products
listed in this document in the
‘‘Discontinued Drug Product List’’
section of the Orange Book. The
‘‘Discontinued Drug Product List’’
identifies, among other items, drug
products that have been discontinued
VerDate Mar<15>2010
15:51 Jul 27, 2011
Jkt 223001
Pfizer Laboratories, Division of Pfizer Inc., 235 East 42nd
St., New York, NY 10017
Do.
Novartis Pharmaceuticals Corp., One Health Plaza, East
Hanover, NJ 07936–1080
GlaxoSmithKline
from marketing for reasons other than
safety or effectiveness.
Approved ANDAs that refer to the
NDAs listed in this document are
unaffected by the discontinued
marketing of the products subject to
those NDAs. Additional ANDAs that
refer to these products may also be
approved by the Agency if they comply
with relevant legal and regulatory
requirements. If FDA determines that
labeling for these drug products should
be revised to meet current standards, the
PO 00000
Frm 00047
Fmt 4703
Sfmt 9990
Agency will advise ANDA applicants to
submit such labeling.
Dated: July 25, 2011.
David Dorsey,
Acting Deputy Commissioner for Policy,
Planning and Budget.
[FR Doc. 2011–19110 Filed 7–27–11; 8:45 am]
BILLING CODE 4160–01–P
E:\FR\FM\28JYN1.SGM
28JYN1
]]>Agencies
[Federal Register Volume 76, Number 145 (Thursday, July 28, 2011)]
[Notices]
[Pages 45262-45267]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-19040]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2011-N-0511]
Agency Information Collection Activities; Proposed Collection;
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 an
opportunity for public comment on the proposed collection of certain
information by the Agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal Agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on the collection of information
requirements relating to FDA's regulation of current good manufacturing
practice (CGMP) and related regulations for blood and blood components;
and requirements for donor testing, donor notification, and
``lookback.''
DATES: Submit either electronic or written comments on the collection
of information by September 26, 2011.
ADDRESSES: Submit electronic comments on the collection of information
to https://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Juanmanuel Vilela, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850, 301-796-7651,
Juanmanuel.vilela@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
Agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR
1320.3(c) and includes Agency requests or requirements that members of
the public submit reports, keep records, or provide information to a
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A))
requires Federal Agencies to provide a 60-day notice in the Federal
Register concerning each proposed collection of information, including
each proposed extension of an existing collection of information,
before submitting the collection to OMB for approval. To comply with
this requirement, FDA is publishing notice of the proposed collection
of information set forth in this document.
With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
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
[[Page 45263]]
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 (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 CGMP and related regulations.
The CGMP regulations (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 (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) (21 CFR 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.
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.
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) (21 CFR 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 (21 CFR 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 for, among other things,
notifying transfusion recipients of blood and blood components, or the
recipient's physician of record or legal
[[Page 45264]]
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 (21 CFR 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 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. 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 the 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. 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
[[Page 45265]]
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. 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 2 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.
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.
610.47(a)(1)(ii)(B) and (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 4,059 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, roughly 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.
[[Page 45266]]
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(a)........................................................ \5\ 288 1.20 346 0.5 173
606.170(b) \2\.................................................... 76 1 76 20 1,520
610.40(c)(1)(ii).................................................. 1,706 2.11 3,600 0.08 288
610.40(g)(2)...................................................... 1 1 1 1 1
610.40(h)(2)(ii)(A)............................................... 1 1 1 1 1
610.40(h)(2)(ii)(C) and (h)(2)(ii)(D)............................. 40 12 480 0.2 96
610.40(h)(2)(vi).................................................. 1,706 10.55 18,000 0.08 1,440
610.42(a)......................................................... 1 1 1 1 1
610.46(a)(1)(ii)(B)............................................... 1,675 6.27 10,500 0.17 1,785
610.46(a)(3)...................................................... 1,675 6.27 10,500 0.17 1,785
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
610.47(a)(3)...................................................... 1,675 13.97 23,400 0.17 3,978
610.47(b)(3)...................................................... 4,059 0.51 2,050 1 2,050
630.6(a) \3\...................................................... 558 775.98 433,000 0.08 34,640
630.6(a) \4\...................................................... 85 52.94 4,500 1.5 6,750
630.6(d)(1)....................................................... 84 31.07 2,610 1 2,610
-------------------------------------------------------------------------------------
Total......................................................... .............. ................. .............. ................. 62,851
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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).
\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.
\5\ 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).
Table 2--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Number of records Total annual Average burden
21 CFR section recordkeepers per recordkeeper records per recordkeeping Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
606.100(b) \2\.................................................... \5\ 288 1 288 24 6,912
606.100(c)........................................................ \5\ 288 10 2,880 1 2,880
606.110(a) \3\.................................................... \6\ 52 1 52 0.5 26
606.151(e)........................................................ \5\ 288 12 3,456 0.08 276
606.160 \4\....................................................... \5\ 288 1,329.86 383,000 0.75 287,250
606.160(b)(1)(viii)
HIV consignee notification.................................... 1,675 12.54 21,000 0.17 3,570
4,059 5.17 21,000 0.17 3,570
HCV consignee notification.................................... 1,675 27.94 46,800 0.17 7,956
4,059 11.53 46,800 0.17 7,956
HIV recipient notification.................................... 4,059 0.43 1,755 0.17 298
HCV recipient notification.................................... 4,059 0.51 2,050 0.17 349
606.160(b)(1)(ix)................................................. 1,706 1,025.79 1,750,000 0.05 87,500
606.160(b)(1)(xi)................................................. 1,675 3.51 5,872 0.05 294
606.165........................................................... \5\ 288 1,329.86 383,000 0.08 30,640
606.170(a)........................................................ \5\ 288 12 3,456 1 3,456
610.40(g)(1)...................................................... 1,706 1 1,706 0.50 853
-------------------------------------------------------------------------------------
Total......................................................... .............. ................. .............. ................. 443,786
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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 the Clinical Laboratory Improvement Amendments of 1988 that transfuse blood and components and FDA-
registered blood establishments (0.05 x 4,059 + 1,706).
\6\ Five percent of plateletpheresis and leukopheresis establishments (0.05 x 1,032).
[[Page 45267]]
Dated: July 22, 2011.
David Dorsey,
Acting Deputy Commissioner for Policy, Planning and Budget.
[FR Doc. 2011-19040 Filed 7-27-11; 8:45 am]
BILLING CODE 4160-01-P
