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 Donation Testing, Donor Notification, and “Lookback”, 16870-16875 [2018-07972]
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Federal Register / Vol. 83, No. 74 / Tuesday, April 17, 2018 / Notices
1. Product name.
2. Application number.
3. Chemical name and structure.
4. Proposed indication(s) or context of
product development.
5. Background section that includes a
brief history of the development
program and the events leading up to
the meeting, and the status of product
development.
6. Proposed agenda, including
estimated times needed for discussion
of each agenda item.
7. List of questions for discussion
with a brief summary for each question
to explain the need or context for the
question.
8. Drug development issue (e.g.,
dosing, clinical trial design, safety
prediction), including the proposed
MIDD approach to the solution,
information to support discussion (e.g.,
a description of the data used for
developing the models, model
development, simulation plan, results),
and how the Agency can help guide any
next steps relative to the regulatory
decision making process, which should
be summarized and clearly articulated
with any supporting data imperative to
the discussion.
E. Meeting Summaries
A meeting summary will be sent to
the requester within 60 days of each
meeting.
IV. Paperwork Reduction Act of 1995
This notice refers to collections of
information that are subject to review by
the Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (44 U.S.C. 3501–3520). The
collection of information resulting from
formal meetings between sponsors or
applicants and FDA has been approved
under OMB control number 0910–0429.
The collection of information in 21 CFR
part 312 (INDs) has been approved
under OMB control number 0910–0014.
Dated: April 12, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–08010 Filed 4–16–18; 8:45 am]
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BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2017–N–6931]
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
Donation Testing, Donor Notification,
and ‘‘Lookback’’
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA, we, or Agency) 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 May 17,
2018.
SUMMARY:
To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0116. Also
include the FDA docket number found
in brackets in the heading of this
document.
ADDRESSES:
Ila
S. Mizrachi, Office of Operations, Food
and Drug Administration, Three White
Flint North, 10A–12M, 11601
Landsdown St., North Bethesda, MD
20852, 301–796–7726, PRAStaff@
fda.hhs.gov.
FOR FURTHER INFORMATION CONTACT:
In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
SUPPLEMENTARY INFORMATION:
Current Good Manufacturing Practices
and Related Regulations for Blood and
Blood Components; and Requirements
for Donation 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
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Service Act (PHS Act) (42 U.S.C.
262(a)). Section 351(a) requires that
manufacturers of biological products,
which include blood and blood
components intended for further
manufacturing into 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 (FD&C Act) also applies to
biological products. Blood and blood
components for transfusion or for
further manufacturing into 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 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), 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 (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 donations for evidence of relevant
transfusion-transmitted infections and
in notifying donors is to prevent the
transmission of relevant transfusiontransmitted infections. For example, the
‘‘lookback’’ requirements are intended
to help ensure the continued safety of
the blood supply by providing necessary
information to consignees of blood and
blood components and appropriate
notification of recipients of blood
components that are at increased risk for
transmitting human immunodeficiency
virus (HIV) or hepatitis C virus (HCV)
infection.
The information collection
requirements in the CGMP, donation
testing, donor notification, and
‘‘lookback’’ regulations provide FDA
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with the necessary information to
perform its duty to ensure the safety,
purity, and potency of blood and blood
components. These requirements
establish accountability and traceability
in the processing and handling of blood
and blood components and enable FDA
to perform meaningful inspections.
The recordkeeping requirements serve
preventive and remedial purposes. The
third-party disclosure requirements
identify 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) (21 CFR 606.170(b)), in
brief, requires that facilities notify
FDA’s Center for Biologics Evaluation
and Research (CBER), as soon as
possible after a complication of blood
collection or transfusion is confirmed to
be fatal. The collecting facility is
required 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 2016, FDA
received 81 fatality reports.
Section 610.40(g)(2) (21 CFR
610.40(g)(2)) requires an establishment
to obtain written approval from FDA to
ship human blood or blood components
for further manufacturing use prior to
completion of testing for evidence of
infection due to relevant transfusiontransmitted infections.
Section 610.41(b) (21 CFR 610.41(b))
allows for a previously deferred donor
to subsequently be found to be an
eligible donor of blood and blood
components by a requalification method
or process found acceptable for such
purposes by FDA.
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 infection due to a
relevant transfusion-transmitted
infection(s) or collected from a donor
deferred under § 610.41(a).
In addition, § 630.35(b) (21 CFR
630.35(b)) allows for a previously
deferred donor, deferred for reasons
other than § 610.41(a), to become
requalified for donation by a method or
process found acceptable for such
purpose by FDA.
Under the third-party disclosure
requirements, § 606.145(c) (21 CFR
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606.145(c)) requires transfusion services
to notify certain blood collection
establishments concerning bacterial
contamination of platelets and other
additional information. In table 3, FDA
estimates that for the approximately
4,961 transfusion services, there would
be 1,400 total notifications per year to
blood collection establishments (700
notifications that platelets are
bacterially contaminated and 700
notifications per year concerning the
identity or non-identity of the species of
the contaminating organism).
Section 610.40(c)(1)(ii), in brief,
requires that each donation dedicated to
a single identified recipient be labeled
as required under § 606.121 (21 CFR
606.121) and with a label containing the
name and identifying information of the
recipient. The information collection
requirements under § 606.121 are part of
usual and customary business practice.
Section 610.40(h)(2)(ii)(C) and (D), in
brief, require an establishment to label
certain reactive human blood and blood
components with the appropriate
screening test results for evidence of
infection due to the identified relevant
transfusion-transmitted infection(s),
and, if they are intended for further
manufacturing use into products, to
include a statement on the label
indicating the exempted use specifically
approved by FDA. Also,
§ 610.40(h)(2)(vi) requires each donation
of human blood or blood components,
excluding Source Plasma, that tests
reactive by a screening test for syphilis
and is determined to be a biological
false positive to be labeled with both
test results.
Section 610.42(a) (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 relevant transfusiontransmitted infection(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 relevant
transfusion-transmitted infection(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
‘‘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 (see §§ 610.46(a)(1) and
610.47(a)(1)). The requirement for ‘‘an
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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
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)). The burden for the
recordkeeping requirements under
§§ 610.46(a) and (b) and 610.47(a) and
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(b) are included under § 606.100 (21
CFR 606.100).
Section 630.40(a) (21 CFR 630.40(a))
requires an establishment to make
reasonable attempts to notify any donor
who has been deferred as required by
§ 610.41(a), or who has been determined
not to be eligible as a donor. Section
630.40(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) (21 CFR
606.110(a)) provides that the use of
plateletpheresis and leukapheresis
procedures to obtain a product for a
specific recipient may be at variance
with the additional standards for that
specific product if, among other things,
the physician determines and
documents 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 the tables of this
document.
Section 606.151(e) (21 CFR
606.151(e)) requires that SOPs for
compatibility testing include procedures
to expedite transfusion in lifethreatening emergencies; records of all
such incidents must be maintained,
including complete documentation
justifying the emergency action, which
must be signed by a physician.
Section 606.171 (21 CFR 606.171)
requires establishments to establish and
maintain procedures related to product
deviations. The burden for the
recordkeeping requirements under
§ 606.171 are included under § 606.100.
So that each significant step in the
collection, processing, compatibility
testing, storage, and distribution of each
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unit of blood and blood components can
be clearly traced, § 606.160 (21 CFR
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)(x) 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. Section 606.170(a) also
requires that when an investigation
determines 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.
Under § 630.15(a)(1)(ii)(B) (21 CFR
630.15(a)(1)(ii)(B)), FDA requires that
for a dedicated donation based on the
intended recipient’s documented
exceptional medical need, the
responsible physician determines and
documents that the health of the donor
would not be adversely affected by
donating.
Under § 630.20(c) (21 CFR 630.20(c)),
a collection establishment may collect
blood and blood components from a
donor who is determined to be not
eligible to donate under any provision
of § 630.10(e) and (f) or § 630.15(a), if
the donation is restricted for use solely
by a specific transfusion recipient based
on documented exceptional medical
need and the responsible physician
determines and documents that the
donor’s health permits the collection
procedure, and that the donation
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presents no undue medical risk to the
transfusion recipient.
In addition to the CGMP regulations
in part 606, the regulations in 21 CFR
part 630 that include requirements for
blood and blood components intended
for transfusion or further manufacturing
use and in 21 CFR part 640 that require
additional standards for certain blood
and blood products are as follows: 21
CFR 630.5(b)(1)(i) and(d); 630.10(c)(1)
and (2); 630.10(f)(2) and (4);
630.10(g)(2)(i); 630.15(a)(1)(ii)(A) and
(B); 630.15(b)(2), (b)(7)(i) and (iii);
630.20(a) and (b); 640.21(e)(4);
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); 640.65(b)(2)(i);
640.66; 640.71(b)(1); 640.72; 640.73; and
640.76(a) and (b). The information
collection requirements and estimated
burdens for these regulations are
included in the part 606 burden
estimates, as described in tables 1 and
2.
Respondents to this collection of
information are licensed and unlicensed
blood establishments that collect blood
and blood components, including
Source Plasma and Source Leukocytes,
inspected by FDA, and transfusion
services inspected by Centers for
Medicare and Medicaid Services (CMS).
Based on information received from
CBER’s database systems, there are
approximately 569 licensed Source
Plasma establishments and
approximately 1,054 licensed blood
collection establishments, for an
estimated total of 1,623 (569 + 1,054)
licensed blood collection
establishments. Also, there are an
estimated total of 680 unlicensed,
registered blood collection
establishments for an approximate total
of 2,303 collection establishments (569
+ 1,054 + 680 = 2,303 establishments).
Of these establishments, approximately
901 perform plateletpheresis and
leukopheresis. These establishments
annually collect approximately 53.3
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 estimated 4,961 establishments
that fall under the Clinical Laboratory
Improvement Amendments of 1988
(CLIA) (formerly referred to as facilities
approved for Medicare reimbursement)
that transfuse blood and blood
components.
The following reporting,
recordkeeping, and disclosure estimates
are based on information provided by
industry, CMS, and FDA experience.
Based on information from industry, we
estimate that there are approximately
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38.3 million donations of Source Plasma
from approximately 2 million donors
and approximately 15 million donations
of Whole Blood and apheresis Red
Blood Cells including approximately
34,500 (approximately 0.23 percent of
15 million) autologous donations, from
approximately 10.9 million donors.
Assuming each autologous donor makes
an average of 1.1 donations, FDA
estimates that there are approximately
31,364 autologous donors (34,500
autologous/1.1 average donations).
FDA estimates that approximately
0.19 percent (21,000/10,794,000) 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 relevant transfusiontransmitted infections. Shipments of
Source Leukocytes are 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.
According to CBER’s database system,
there are approximately 15 licensed
manufacturers that ship known reactive
human blood or blood components
under § 610.40(h)(2)(ii)(C) and (D). FDA
estimates that each manufacturer would
ship an estimated 1 unit of human blood
or blood components per month (12 per
year) that would require two labels; one
as reactive for the appropriate screening
test under § 610.40(h)(2)(ii)(C), and the
other stating the exempted use
specifically approved by FDA under
§ 610.40(h)(2)(ii)(D).
Based on information received from
industry, we estimate that
approximately 7,544 donations will test
reactive by a screening test for syphilis
and be determined to be biological false
positives by additional testing annually.
These units would be labeled according
to § 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
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indicating that the product was
manufactured from a donation found to
be reactive for the identified relevant
transfusion-transmitted infection(s). 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
3,021 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 9,063
(3,021 × 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
9,063 (3,021 × 3) notifications to
consignees of subsequent test results.
We estimate that approximately 4,961
consignees will be required under
§ 610.46(b)(3) to notify transfusion
recipients, their legal representatives, or
physicians of record an average of 0.35
times per year resulting in a total
number of 1,755 (585 confirmed
positive repeat donors × 3) notifications.
Also under § 610.46(b)(3), we estimate
and include the time to gather test
results and records for each recipient
and to accommodate multiple attempts
to contact the recipient.
Furthermore, we estimate that
approximately 6,799 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 two times for each
of the 20,397 (6,799 × 3 components)
components prepared from these
donations, once for quarantine purposes
and again with additional HCV test
results for a total of 40,794 (20,397 × 2)
notifications as an annual ongoing
burden. Under § 610.47(b)(3), we
estimate that approximately 4,961
consignees would notify approximately
2,050 recipients or their physicians of
record annually.
Based on industry estimates,
approximately 14.3 percent of
approximately 9 million potential
donors (1,287,000 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 1,734 (1,054 + 680) blood
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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
(1,156) of the 1,734 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 approximately onethird, or 578 of the 1,734 blood
collecting establishments would need to
provide, under § 630.40(a), additional
information and onsite counseling to the
estimated 429,000 (one-third of
approximately 1,287,000) ineligible
donors.
It is estimated that another 4.5 percent
of 10 million potential donors (450,000
donors) are deferred annually based on
test results. We estimate that
approximately 95 percent of the
establishments that collect 99 percent of
the blood and blood components notify
donors who have reactive test results for
HIV, hepatitis B virus, HCV, human Tlymphotropic virus, and syphilis as
usual and customary business practice.
Consequently, 5 percent of the 1,623
licensed establishments (81) collecting 1
percent (4,050) of the deferred donors
(405,000) would notify donors under
§ 630.40(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 § 630.40(d)(1).
However, we estimate that
approximately 5 percent of the 1,054
blood collection establishments (53)
may not notify the referring physicians
of the estimated 2 percent of 31,364
autologous donors with the initial
reactive test results (627) 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)(x), we estimate
the total annual records based on the
approximately 1,287,000 donors
determined not to be eligible to donate
and each of the estimated 1,692,000
(1,287,000 + 405,000) donors deferred
based on reactive test results for
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evidence of infection because of
relevant transfusion-transmitted
infections. Under § 606.160(b)(1)(xi),
only the 1,734 registered blood
establishments collect autologous
donations and, therefore, are required to
notify referring physicians. We estimate
that 4.5 percent of the 31,364 autologous
donors (1,411) will be deferred under
§ 610.41, which in turn will lead to the
notification of their referring physicians.
Under § 610.41(b), FDA estimates that
there would be 25 submissions for
requalification of donors. In addition,
FDA estimates that there would be only
three notifications for requalification of
donors under § 630.35(b). FDA also
estimates the average time for each
submission.
FDA permits the shipment of untested
or incompletely tested human blood or
blood components in rare medical
emergencies and when appropriately
documented (§ 610.40(g)(1)). 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) is part of the usual and
customary business practice of blood
establishments.
In the Federal Register of January 23,
2018 (83 FR 3165), FDA published a 60-
day notice requesting public comment
on the proposed collection of
information. Although one comment
was received, it was not responsive to
the four collection of information topics
solicited and therefore will not be
discussed in this document.
The average burden per response
(hours) and average burden per
recordkeeping (hours) are based on
estimates received from industry or FDA
experience with similar reporting or
recordkeeping requirements.
FDA estimates the burden of this
collection of information as follows:
TABLE 1—ESTIMATED ANNUAL REPORTING BURDEN 1
Number of
respondents
21 CFR section
Number of
responses per
respondent
Total annual
responses
Average
burden per
response
Total hours
606.170(b) 2 ..........................................................................
610.40(g)(2) .........................................................................
610.41(b) ..............................................................................
610.40(h)(2)(ii)(A) .................................................................
630.35(b) ..............................................................................
81
1
1,623
1
1,623
1
1
0.015
1
0.002
81
1
25
1
3
20
1
7
1
7
1,620
1
175
1
21
Total ..............................................................................
........................
........................
........................
........................
1,818
1 There
2 The
are no capital costs or operating and maintenance costs associated with this collection of information.
reporting requirement in § 640.73, which addresses the reporting of fatal donor reactions, is included in the estimate for § 606.170(b).
TABLE 2—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1
Number of
recordkeepers
21 CFR section/activity
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 .....................
Number of
records per
recordkeeper
5 363
Total annual
records
Average
burden per
recordkeeping
5 363
1,734
1
10
1
12
1,055.096
10.4533
363
3,630
45
4,356
383,000
18,126
606.160(b)(1)(viii) HCV consignee notification ....................
4,961
1,734
3.6537
23.5259
18,126
40,794
HIV recipient notification ......................................................
HCV recipient notification ....................................................
606.160(b)(1)(x) ...................................................................
606.160(b)(1)(xi) ..................................................................
606.165 ................................................................................
606.170(a) ...........................................................................
610.40(g)(1) .........................................................................
630.15(a)(1)(ii)(B) ................................................................
630.20(c) ..............................................................................
4,961
4,961
4,961
2,303
1,734
5 363
5 363
2,303
1,734
1,734
8.2229
0.3538
0.4132
734.6939
0.8137
1,055.096
12
1
1
1
40,794
1,755
2,050
1,692,000
1,411
383,000
4,356
2,303
1,734
1,734
0.17 (10 min.)
0.17 (10 min.)
0.05 (3 min.) ..
0.05 (3 min.) ..
0.08 (5 min.) ..
1 .....................
0.5 (30 min.) ..
1 .....................
1 .....................
6,935
298
349
84,600
71
30,640
4,356
1,152
1,734
1,734
Total ..............................................................................
........................
........................
........................
........................
444,930
5 363
6 45
5 363
1 There
0.17 (10 min.)
0.17 (10 min)
8,712
3,630
23
348
287,250
3,081
3,081
6,935
are no capital costs or operating and maintenance costs associated with this collection of information.
recordkeeping requirements in §§ 606.171, 610.46(a) and (b), 610.47(a) and (b), 630.5(d), 630.10(c)(1) and (2), 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 §§ 606.110(a)(2); 630.5(b)(1)(i); 630.109(f)(2) and (4); 630.10(g)(2)(i); 630.15(a)(1)(ii)(A) and (B);
630.15(b)(2), (b)(7)(i) and (iii); 630.20(a) and (b); 640.21(e)(4); 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); 630.15(b)(2); 640.65(b)(2)(i); 640.71(b)(1); 640.72; 640.73; and 640.76(a) and (b), which address the maintenance of various
records are included in the estimate for § 606.160.
5 Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 ×
4,961 + 2,303 = 363).
6 Five percent of plateletpheresis and leukopheresis establishments (0.05 × 901 = 45).
2 The
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1 .....................
0.5 (30 min) ...
0.08 (5 min.) ..
0.75 (45 min.)
0.17 (10 min.)
0.17 (10 min.)
Total hours
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16875
TABLE 3—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
respondents
21 CFR section
Number of
disclosures
per
respondent
Total annual
disclosures
Average
burden per
disclosure
Total hours
606.145(c) ............................................................................
606.170(a) ...........................................................................
610.40(c)(1)(ii) .....................................................................
610.40(h)(2)(ii)(C) and (h)(2)(ii)(D) ......................................
610.40(h)(2)(vi) ....................................................................
610.42(a) .............................................................................
610.46(a)(1)(ii)(B) ................................................................
610.46(a)(3) .........................................................................
610.46(b)(3) .........................................................................
610.47(a)(1)(ii)(B) ................................................................
610.47(a)(3) .........................................................................
610.47(b)(3) .........................................................................
630.40(a) 3 ...........................................................................
630.40(a) 4 ...........................................................................
630.40(d)(1) .........................................................................
4,961
2 363
2,303
15
2,303
1
1,734
1,734
4,961
1,734
1,734
4,961
578
81
53
0.2822
12
0.0595
12
3.28
1
5.2266
5.2266
0.3538
11.7630
11.7630
0.4132
742.214
50
11.83
1,400
4,356
137
180
7,554
1
9,063
9,063
1,755
20,397
20,397
2,050
429,000
4,050
627
0.02 ................
0.5 (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.) ..
1.5 ..................
1 .....................
28
2,178
11
36
604
1
1,541
1,541
1,755
3,467
3,467
2,050
34,320
6,075
627
Total ..............................................................................
........................
........................
........................
........................
57,701
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered blood establishments (0.05 ×
4,961 + 2,303 = 363).
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 relevant transfusion-transmitted infections.
2 Five
The burden for this information
collection has changed since the last
OMB approval. Because of a slight
decrease in the number of blood
establishments during the last 3 years,
FDA has decreased our recordkeeping
and third-party disclosure burden
estimates.
Dated: April 12, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–07972 Filed 4–16–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
Advisory Committee on Training in
Primary Care Medicine and Dentistry
Health Resources and Service
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice of Federal Advisory
Committee meeting.
AGENCY:
In accordance with the
Federal Advisory Committee Act, this
notice announces that the Advisory
Committee on Training in Primary Care
Medicine and Dentistry (ACTPCMD)
will hold a public meeting.
DATES: Thursday, May 3, 2018, from
8:30 a.m. to 5:00 p.m. and Friday, May
4, 2018, from 8:30 a.m. to 2:00 p.m. ET.
ADDRESSES: The address for the meeting
is 5600 Fishers Lane, Rockville,
daltland on DSKBBV9HB2PROD with NOTICES
SUMMARY:
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Maryland 20857, Room 5E29. The
conference call-in number: 1–800–857–
9729 and Passcode: 1318150. The
webinar link is https://
hrsa.connectsolutions.com/actpcmd.
FOR FURTHER INFORMATION CONTACT:
Anyone requesting information
regarding the ACTPCMD should contact
Dr. Kennita R. Carter, Designated
Federal Official (DFO), Division of
Medicine and Dentistry, Bureau of
Health Workforce, HRSA, in one of
three ways: (1) Send a request to the
following address: Dr. Kennita R. Carter,
DFO, Division of Medicine and
Dentistry, HRSA, 5600 Fishers Lane,
Room 15N–116, Rockville, MD 20857;
(2) call 301–945–3505; or (3) send an
email to KCarter@hrsa.gov.
SUPPLEMENTARY INFORMATION:
ACTPCMD provides advice and
recommendations to the Secretary of the
Department of Health and Human
Services on policy, program
development, and other matters of
significance concerning the activities
under section 747 of Title VII of the
Public Health Service Act (PHSA).
ACTPCMD prepares an annual report
describing the activities of the
Committee, including findings and
recommendations made by the
Committee concerning the activities
under section 747, as well as training
programs in oral health and dentistry.
The annual report is submitted to the
Secretary and ranking members of the
Senate Committee on Health, Education,
Labor and Pensions, and the House of
Representatives Committee on Energy
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and Commerce. The Committee also
develops, publishes, and implements
performance measures and guidelines
for longitudinal evaluations of programs
authorized under Title VII, Part C, of the
PHSA, and recommends appropriation
levels for programs under this Part.
During the May 3–4, 2018, meeting,
ACTPCMD will review the impact of the
Title VII, Section 747 and oral health
training programs, and make
recommendations on funding and
appropriation levels. In addition, the
Committee will identify its strategic
priorities for the coming year, and
discuss issues related to pending
Committee reports on the integration of
behavioral health into primary care and
oral health training, and clinical trainee
and faculty well-being and resilience.
Information about ACTPCMD and the
agenda for this meeting is located on the
ACTPCMD website at https://
www.hrsa.gov/advisory-committees/
primarycare-dentist/. Please
note that agenda items are subject to
change as priorities dictate.
Members of the public will have the
opportunity to provide comments.
Public participants may submit written
statements in advance of the scheduled
meeting. Oral comments will be
honored in the order they are requested
and may be limited as time allows.
Requests to make oral comments or
provide written comments to the
ACTPCMD should be sent to Dr. Carter,
DFO, using the contact information
above at least three business days prior
to the meeting.
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]]>Agencies
[Federal Register Volume 83, Number 74 (Tuesday, April 17, 2018)]
[Notices]
[Pages 16870-16875]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-07972]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2017-N-6931]
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 Donation Testing, Donor Notification,
and ``Lookback''
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, we, or Agency) 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 May 17,
2018.
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 [email protected]. 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, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852, 301-796-7726,
[email protected].
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 Donation Testing, Donor
Notification, and ``Lookback''
OMB Control Number 0910-0116--Extension
All blood and blood components introduced or delivered for
introduction into interstate commerce are subject to section 351(a) of
the Public Health Service Act (PHS Act) (42 U.S.C. 262(a)). Section
351(a) requires that manufacturers of biological products, which
include blood and blood components intended for further manufacturing
into 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 (FD&C Act) also applies to biological products. Blood
and blood components for transfusion or for further manufacturing into
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 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), 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 (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 donations for evidence of relevant
transfusion-transmitted infections and in notifying donors is to
prevent the transmission of relevant transfusion-transmitted
infections. For example, the ``lookback'' requirements are intended to
help ensure the continued safety of the blood supply by providing
necessary information to consignees of blood and blood components and
appropriate notification of recipients of blood components that are at
increased risk for transmitting human immunodeficiency virus (HIV) or
hepatitis C virus (HCV) infection.
The information collection requirements in the CGMP, donation
testing, donor notification, and ``lookback'' regulations provide FDA
[[Page 16871]]
with the necessary information to perform its duty to ensure the
safety, purity, and potency of blood and blood components. These
requirements establish accountability and traceability in the
processing and handling of blood and blood components and enable FDA to
perform meaningful inspections.
The recordkeeping requirements serve preventive and remedial
purposes. The third-party disclosure requirements identify 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) (21 CFR
606.170(b)), in brief, requires that facilities notify FDA's Center for
Biologics Evaluation and Research (CBER), as soon as possible after a
complication of blood collection or transfusion is confirmed to be
fatal. The collecting facility is required 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 2016, FDA received 81 fatality reports.
Section 610.40(g)(2) (21 CFR 610.40(g)(2)) requires an
establishment to obtain written approval from FDA to ship human blood
or blood components for further manufacturing use prior to completion
of testing for evidence of infection due to relevant transfusion-
transmitted infections.
Section 610.41(b) (21 CFR 610.41(b)) allows for a previously
deferred donor to subsequently be found to be an eligible donor of
blood and blood components by a requalification method or process found
acceptable for such purposes by FDA.
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
infection due to a relevant transfusion-transmitted infection(s) or
collected from a donor deferred under Sec. 610.41(a).
In addition, Sec. 630.35(b) (21 CFR 630.35(b)) allows for a
previously deferred donor, deferred for reasons other than Sec.
610.41(a), to become requalified for donation by a method or process
found acceptable for such purpose by FDA.
Under the third-party disclosure requirements, Sec. 606.145(c) (21
CFR 606.145(c)) requires transfusion services to notify certain blood
collection establishments concerning bacterial contamination of
platelets and other additional information. In table 3, FDA estimates
that for the approximately 4,961 transfusion services, there would be
1,400 total notifications per year to blood collection establishments
(700 notifications that platelets are bacterially contaminated and 700
notifications per year concerning the identity or non-identity of the
species of the contaminating organism).
Section 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 (21 CFR 606.121) and with a label containing the name and
identifying information of the recipient. The information collection
requirements under Sec. 606.121 are part of usual and customary
business practice.
Section 610.40(h)(2)(ii)(C) and (D), in brief, require an
establishment to label certain reactive human blood and blood
components with the appropriate screening test results for evidence of
infection due to the identified relevant transfusion-transmitted
infection(s), and, if they are intended for further manufacturing use
into products, to include a statement on the label indicating the
exempted use specifically approved by FDA. Also, Sec. 610.40(h)(2)(vi)
requires each donation of human blood or blood components, excluding
Source Plasma, that tests reactive by a screening test for syphilis and
is determined to be a biological false positive to be labeled with both
test results.
Section 610.42(a) (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 relevant transfusion-transmitted infection(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 relevant transfusion-transmitted infection(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 ``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
(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 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)). The burden for the recordkeeping
requirements under Sec. Sec. 610.46(a) and (b) and 610.47(a) and
[[Page 16872]]
(b) are included under Sec. 606.100 (21 CFR 606.100).
Section 630.40(a) (21 CFR 630.40(a)) requires an establishment to
make reasonable attempts to notify any donor who has been deferred as
required by Sec. 610.41(a), or who has been determined not to be
eligible as a donor. Section 630.40(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) (21 CFR 606.110(a)) provides that the
use of plateletpheresis and leukapheresis procedures to obtain a
product for a specific recipient may be at variance with the additional
standards for that specific product if, among other things, the
physician determines and documents 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 the
tables of this document.
Section 606.151(e) (21 CFR 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.
Section 606.171 (21 CFR 606.171) requires establishments to
establish and maintain procedures related to product deviations. The
burden for the recordkeeping requirements under Sec. 606.171 are
included under Sec. 606.100.
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 (21 CFR
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)(x) 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. Section 606.170(a) also requires that
when an investigation determines 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.
Under Sec. 630.15(a)(1)(ii)(B) (21 CFR 630.15(a)(1)(ii)(B)), FDA
requires that for a dedicated donation based on the intended
recipient's documented exceptional medical need, the responsible
physician determines and documents that the health of the donor would
not be adversely affected by donating.
Under Sec. 630.20(c) (21 CFR 630.20(c)), a collection
establishment may collect blood and blood components from a donor who
is determined to be not eligible to donate under any provision of Sec.
630.10(e) and (f) or Sec. 630.15(a), if the donation is restricted for
use solely by a specific transfusion recipient based on documented
exceptional medical need and the responsible physician determines and
documents that the donor's health permits the collection procedure, and
that the donation presents no undue medical risk to the transfusion
recipient.
In addition to the CGMP regulations in part 606, the regulations in
21 CFR part 630 that include requirements for blood and blood
components intended for transfusion or further manufacturing use and in
21 CFR part 640 that require additional standards for certain blood and
blood products are as follows: 21 CFR 630.5(b)(1)(i) and(d);
630.10(c)(1) and (2); 630.10(f)(2) and (4); 630.10(g)(2)(i);
630.15(a)(1)(ii)(A) and (B); 630.15(b)(2), (b)(7)(i) and (iii);
630.20(a) and (b); 640.21(e)(4); 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);
640.65(b)(2)(i); 640.66; 640.71(b)(1); 640.72; 640.73; and 640.76(a)
and (b). The information collection requirements and estimated burdens
for these regulations are included in the part 606 burden estimates, as
described in tables 1 and 2.
Respondents to this collection of information are licensed and
unlicensed blood establishments that collect blood and blood
components, including Source Plasma and Source Leukocytes, inspected by
FDA, and transfusion services inspected by Centers for Medicare and
Medicaid Services (CMS). Based on information received from CBER's
database systems, there are approximately 569 licensed Source Plasma
establishments and approximately 1,054 licensed blood collection
establishments, for an estimated total of 1,623 (569 + 1,054) licensed
blood collection establishments. Also, there are an estimated total of
680 unlicensed, registered blood collection establishments for an
approximate total of 2,303 collection establishments (569 + 1,054 + 680
= 2,303 establishments). Of these establishments, approximately 901
perform plateletpheresis and leukopheresis. These establishments
annually collect approximately 53.3 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 estimated 4,961 establishments that fall under the Clinical
Laboratory Improvement Amendments of 1988 (CLIA) (formerly referred to
as facilities approved for Medicare reimbursement) that transfuse blood
and blood components.
The following reporting, recordkeeping, and disclosure estimates
are based on information provided by industry, CMS, and FDA experience.
Based on information from industry, we estimate that there are
approximately
[[Page 16873]]
38.3 million donations of Source Plasma from approximately 2 million
donors and approximately 15 million donations of Whole Blood and
apheresis Red Blood Cells including approximately 34,500 (approximately
0.23 percent of 15 million) autologous donations, from approximately
10.9 million donors. Assuming each autologous donor makes an average of
1.1 donations, FDA estimates that there are approximately 31,364
autologous donors (34,500 autologous/1.1 average donations).
FDA estimates that approximately 0.19 percent (21,000/10,794,000)
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 relevant transfusion-transmitted
infections. Shipments of Source Leukocytes are 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.
According to CBER's database system, there are approximately 15
licensed manufacturers that ship known reactive human blood or blood
components under Sec. 610.40(h)(2)(ii)(C) and (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).
Based on information received from industry, we estimate that
approximately 7,544 donations will test reactive by a screening test
for syphilis and be determined to be biological false positives by
additional testing annually. These units would be labeled according to
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 indicating that the
product was manufactured from a donation found to be reactive for the
identified relevant transfusion-transmitted infection(s). 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 3,021 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 9,063 (3,021 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 9,063 (3,021 x 3) notifications
to consignees of subsequent test results.
We estimate that approximately 4,961 consignees will be required
under Sec. 610.46(b)(3) to notify transfusion recipients, their legal
representatives, or physicians of record an average of 0.35 times per
year resulting in a total number of 1,755 (585 confirmed positive
repeat donors x 3) notifications. Also under Sec. 610.46(b)(3), we
estimate and include the time to gather test results and records for
each recipient and to accommodate multiple attempts to contact the
recipient.
Furthermore, we estimate that approximately 6,799 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 two times for each of the 20,397 (6,799 x 3 components)
components prepared from these donations, once for quarantine purposes
and again with additional HCV test results for a total of 40,794
(20,397 x 2) notifications as an annual ongoing burden. Under Sec.
610.47(b)(3), we estimate that approximately 4,961 consignees would
notify approximately 2,050 recipients or their physicians of record
annually.
Based on industry estimates, approximately 14.3 percent of
approximately 9 million potential donors (1,287,000 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 1,734 (1,054
+ 680) blood collecting establishments to notify onsite and to explain
why the donor is determined not to be suitable for donating. Based on
such available information, we estimate that two-thirds (1,156) of the
1,734 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 approximately one-third, or 578 of the 1,734 blood
collecting establishments would need to provide, under Sec. 630.40(a),
additional information and onsite counseling to the estimated 429,000
(one-third of approximately 1,287,000) ineligible donors.
It is estimated that another 4.5 percent of 10 million potential
donors (450,000 donors) are deferred annually based on test results. We
estimate that approximately 95 percent of the establishments that
collect 99 percent of the blood and blood components notify donors who
have reactive test results for HIV, hepatitis B virus, HCV, human T-
lymphotropic virus, and syphilis as usual and customary business
practice. Consequently, 5 percent of the 1,623 licensed establishments
(81) collecting 1 percent (4,050) of the deferred donors (405,000)
would notify donors under Sec. 630.40(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. 630.40(d)(1). However, we estimate that approximately 5
percent of the 1,054 blood collection establishments (53) may not
notify the referring physicians of the estimated 2 percent of 31,364
autologous donors with the initial reactive test results (627) 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)(x), we estimate the total annual records
based on the approximately 1,287,000 donors determined not to be
eligible to donate and each of the estimated 1,692,000 (1,287,000 +
405,000) donors deferred based on reactive test results for
[[Page 16874]]
evidence of infection because of relevant transfusion-transmitted
infections. Under Sec. 606.160(b)(1)(xi), only the 1,734 registered
blood establishments collect autologous donations and, therefore, are
required to notify referring physicians. We estimate that 4.5 percent
of the 31,364 autologous donors (1,411) will be deferred under Sec.
610.41, which in turn will lead to the notification of their referring
physicians.
Under Sec. 610.41(b), FDA estimates that there would be 25
submissions for requalification of donors. In addition, FDA estimates
that there would be only three notifications for requalification of
donors under Sec. 630.35(b). FDA also estimates the average time for
each submission.
FDA permits the shipment of untested or incompletely tested human
blood or blood components in rare medical emergencies and when
appropriately documented (Sec. 610.40(g)(1)). 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) is part of the usual and customary business practice of
blood establishments.
In the Federal Register of January 23, 2018 (83 FR 3165), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. Although one comment was received, it was
not responsive to the four collection of information topics solicited
and therefore will not be discussed in this document.
The average burden per response (hours) and average burden per
recordkeeping (hours) are based on estimates received from industry or
FDA experience with similar reporting or recordkeeping requirements.
FDA estimates the burden of this collection of information as
follows:
Table 1--Estimated Annual Reporting Burden 1
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of responses per Total annual Average burden Total hours
respondents respondent responses per response
----------------------------------------------------------------------------------------------------------------
606.170(b) \2\.................. 81 1 81 20 1,620
610.40(g)(2).................... 1 1 1 1 1
610.41(b)....................... 1,623 0.015 25 7 175
610.40(h)(2)(ii)(A)............. 1 1 1 1 1
630.35(b)....................... 1,623 0.002 3 7 21
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 1,818
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ The reporting requirement in Sec. 640.73, which addresses the reporting of fatal donor reactions, is
included in the estimate for Sec. 606.170(b).
Table 2--Estimated Annual Recordkeeping Burden 1
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section/activity Number of records per Total annual Average burden per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
606.100(b) \2\.............. \5\ 363 1 363 24................ 8,712
606.100(c).................. \5\ 363 10 3,630 1................. 3,630
606.110(a) \3\.............. \6\ 45 1 45 0.5 (30 min)...... 23
606.151(e).................. \5\ 363 12 4,356 0.08 (5 min.)..... 348
606.160 \4\................. \5\ 363 1,055.096 383,000 0.75 (45 min.).... 287,250
606.160(b)(1)(viii) HIV 1,734 10.4533 18,126 0.17 (10 min.).... 3,081
consignee notification. .............. .............. .............. 0.17 (10 min.).... ..............
4,961 3.6537 18,126 3,081
606.160(b)(1)(viii) HCV 1,734 23.5259 40,794 0.17 (10 min.).... 6,935
consignee notification. .............. .............. .............. 0.17 (10 min)..... ..............
4,961 8.2229 40,794 6,935
HIV recipient notification.. 4,961 0.3538 1,755 0.17 (10 min.).... 298
HCV recipient notification.. 4,961 0.4132 2,050 0.17 (10 min.).... 349
606.160(b)(1)(x)............ 2,303 734.6939 1,692,000 0.05 (3 min.)..... 84,600
606.160(b)(1)(xi)........... 1,734 0.8137 1,411 0.05 (3 min.)..... 71
606.165..................... \5\ 363 1,055.096 383,000 0.08 (5 min.)..... 30,640
606.170(a).................. \5\ 363 12 4,356 1................. 4,356
610.40(g)(1)................ 2,303 1 2,303 0.5 (30 min.)..... 1,152
630.15(a)(1)(ii)(B)......... 1,734 1 1,734 1................. 1,734
630.20(c)................... 1,734 1 1,734 1................. 1,734
-----------------------------------------------------------------------------------
Total................... .............. .............. .............. .................. 444,930
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ The recordkeeping requirements in Sec. Sec. 606.171, 610.46(a) and (b), 610.47(a) and (b), 630.5(d),
630.10(c)(1) and (2), 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. 606.110(a)(2); 630.5(b)(1)(i); 630.109(f)(2) and (4);
630.10(g)(2)(i); 630.15(a)(1)(ii)(A) and (B); 630.15(b)(2), (b)(7)(i) and (iii); 630.20(a) and (b);
640.21(e)(4); 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);
630.15(b)(2); 640.65(b)(2)(i); 640.71(b)(1); 640.72; 640.73; and 640.76(a) and (b), which address the
maintenance of various records are included in the estimate for Sec. 606.160.
\5\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered
blood establishments (0.05 x 4,961 + 2,303 = 363).
\6\ Five percent of plateletpheresis and leukopheresis establishments (0.05 x 901 = 45).
[[Page 16875]]
Table 3--Estimated Annual Third-Party Disclosure Burden 1
----------------------------------------------------------------------------------------------------------------
Number of
21 CFR section Number of disclosures Total annual Average burden per Total hours
respondents per respondent disclosures disclosure
----------------------------------------------------------------------------------------------------------------
606.145(c).................. 4,961 0.2822 1,400 0.02.............. 28
606.170(a).................. \2\ 363 12 4,356 0.5 (30 min.)..... 2,178
610.40(c)(1)(ii)............ 2,303 0.0595 137 0.08 (5 min.)..... 11
610.40(h)(2)(ii)(C) and 15 12 180 0.20 (12 min.).... 36
(h)(2)(ii)(D).
610.40(h)(2)(vi)............ 2,303 3.28 7,554 0.08 (5 min.)..... 604
610.42(a)................... 1 1 1 1................. 1
610.46(a)(1)(ii)(B)......... 1,734 5.2266 9,063 0.17 (10 min.).... 1,541
610.46(a)(3)................ 1,734 5.2266 9,063 0.17 (10 min.).... 1,541
610.46(b)(3)................ 4,961 0.3538 1,755 1................. 1,755
610.47(a)(1)(ii)(B)......... 1,734 11.7630 20,397 0.17 (10 min.).... 3,467
610.47(a)(3)................ 1,734 11.7630 20,397 0.17 (10 min.).... 3,467
610.47(b)(3)................ 4,961 0.4132 2,050 1................. 2,050
630.40(a) \3\............... 578 742.214 429,000 0.08 (5 min.)..... 34,320
630.40(a) \4\............... 81 50 4,050 1.5............... 6,075
630.40(d)(1)................ 53 11.83 627 1................. 627
-----------------------------------------------------------------------------------
Total................... .............. .............. .............. .................. 57,701
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Five percent of establishments that fall under CLIA that transfuse blood and components and FDA-registered
blood establishments (0.05 x 4,961 + 2,303 = 363).
\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 relevant
transfusion-transmitted infections.
The burden for this information collection has changed since the
last OMB approval. Because of a slight decrease in the number of blood
establishments during the last 3 years, FDA has decreased our
recordkeeping and third-party disclosure burden estimates.
Dated: April 12, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-07972 Filed 4-16-18; 8:45 am]
BILLING CODE 4164-01-P
