[Federal Register Volume 75, Number 47 (Thursday, March 11, 2010)]
[Notices]
[Pages 11545-11549]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-5229]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2010-N-0101]
Agency Information Collection Activities; Proposed Collection;
Comment Request; Human Cells, Tissues, and Cellular and Tissue-Based
Products: Establishment Registration and Listing; Form FDA 3356;
Eligibility Determination for Donors; and Current Good Tissue Practice
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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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 information collection
requirements for FDA regulations related to human cells, tissues, and
cellular and tissue-based products (HCT[sol]Ps) involving establishment
registration and listing using Form FDA 3356; eligibility determination
for donors; and current good tissue practice (CGTP).
DATES: Submit written or electronic comments on the collection of
information by May 10, 2010.
ADDRESSES: Submit electronic comments on the collection of information
to http://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: Elizabeth Berbakos, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850, 301-796-3792.
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)
[[Page 11546]]
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.
Human Cells, Tissues, and Cellular and Tissue-Based Products:
Establishment Registration and Listing; Form FDA 3356; Eligibility
Determination for Donors; and Current Good Tissue Practice--(OMB
Control Number 0910-0543)--Extension
Under section 361 of the Public Health Service Act (the PHS Act)
(42 U.S.C. 264), FDA may issue and enforce regulations necessary to
prevent the introduction, transmission, or spread of communicable
diseases between the States or possessions or from foreign countries
into the States. As derivatives of the human body, all HCT[sol]Ps pose
some risk of carrying pathogens that could potentially infect
recipients or handlers. FDA has issued regulations related to
HCT[sol]Ps involving establishment registration and listing using Form
FDA 3356, eligibility determination for donors, and CGTP.
A. Establishment Registration and Listing; Form FDA 3356
The regulations in part 1271 (21 CFR part 1271) require domestic
and foreign establishments that recover, process, store, label,
package, or distribute an HCT[sol]P described in Sec. 1271.10(a), or
that perform screening or testing of the cell or tissue donor to
register with FDA (Sec. 1271.10(b)(1)) and submit a list of each
HCT[sol]P manufactured (Sec. 1271.10(b)). Section 1271.21(a) requires
an establishment to follow certain procedures for initial registration
and listing of HCT[sol]Ps, and Sec. 1271.25(a) and (b) identifies the
required initial registration and HCT[sol]P listing information.
Section 1271.21(b), in brief, requires an annual update of the
establishment registration. Section 1271.21(c)(ii) requires
establishments to submit HCT[sol]P listing updates when an HCT[sol]P is
changed as described in Sec. 1271.25(c). Section 1271.25(c) identifies
the required HCT[sol]P listing update information. Section 1271.26
requires establishments to submit an amendment if ownership or location
of the establishment changes. FDA requires the use of a registration
and listing form (Form FDA 3356: Establishment Registration and Listing
for Human Cells, Tissues, and Cellular and Tissue-Based Products
(HCT[sol]Ps)) to submit the required information (Sec. Sec. 1271.10,
1271.21, 1271.25, and 1271.26). To further facilitate the ease and
speed of submissions, electronic submission is accepted (http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/EstablishmentRegistration/TissueEstablishmentRegistration/default.htm).
B. Eligibility Determination for Donors
In brief, FDA requires certain HCT[sol]P establishments described
in Sec. 1271.1(b) to determine donor eligibility based on donor
screening and testing for relevant communicable diseases agents and
diseases, except as provided under Sec. 1271.90. The documented
determination of a donor's eligibility is made by a responsible person
defined in Sec. 1271.3(t) and is based on the results of required
donor screening, which includes a donor medical history interview
(defined in Sec. 1271.3(n)) and testing (Sec. 1271.50(a)). Certain
records must accompany an HCT[sol]P once the donor-eligibility
determination has been made (Sec. 1271.55(a)). This requirement
applies both to an HCT[sol]P from a donor who is determined to be
eligible as well as to an HCT[sol]P from a donor who is determined to
be ineligible or where the donor-eligibility determination is not
complete if there is a documented urgent medical need (Sec. 1271.60).
Once the donor-eligibility determination has been made, the HCT[sol]P
must be accompanied by a summary of records used to make the donor-
eligibility determination (Sec. 1271.55(b)) and a statement whether,
based on the results of the screening and testing, the donor is
determined to be eligible or ineligible (Sec. 1271.55(a)(2)).
Records used in determining the eligibility of a donor, i.e.,
results and interpretations of testing for relevant communicable
disease agents, the donor-eligibility determination, the name and
address of the testing laboratory or laboratories, and the name of the
responsible person (defined in Sec. 1271.3(t)) who made the donor-
eligibility determination and the date of the determination, must be
maintained (Sec. 1271.55(d)(1)). If any information on the donor is
not in English, the original record must be retained and translated to
English and accompanied by a statement of authenticity from the
translator (Sec. 1271.55(d)(2)). HCT[sol]P establishments must retain
the records pertaining to HCT[sol]Ps at least 10 years after the date
of administration, distribution, disposition, or expiration, whichever
is latest (Sec. 1271.55(d)(4)).
When a product is shipped in quarantine as defined in Sec.
1271.3(q), before completion of screening and testing, the HCT[sol]P
must be accompanied by records identifying the donor; stating that the
donor-eligibility determination has not been completed; and stating
that the product must not be used until the donor-eligibility
determination has been completed (Sec. 1271.60(c)). When an HCT[sol]P
is used in cases of documented urgent medical need, the results of any
completed donor screening and testing, and a list of any required
screening and testing not yet completed also must accompany the
HCT[sol]P (Sec. 1271.60(d)(2)). When an HCT[sol]P is used in cases of
urgent medical need or from a donor who has been determined to be
ineligible (as permitted under Sec. 1271.65), documentation by the
HCT[sol]P establishment is required showing that the recipient's
physician received notification that the testing and screening were not
complete (in cases of urgent medical need), and upon the completion of
the donor-eligibility determination, of the results of the
determination (Sec. 1271.60(d)(3) and (d)(4) and Sec. 1271.65(b)(3)).
An HCT[sol]P establishment is also required to establish and
maintain procedures for all steps that are performed in determining
eligibility (Sec. 1271.47(a)), including the use of a product from a
donor testing reactive for cytomegalovirus (Sec. 1271.85(b)(2)). The
HCT[sol]P establishment must record any departure from the procedures
(Sec. 1271.47(d)).
C. Current Good Tissue Practice (CGTP)
FDA requires certain HCT[sol]P establishments to follow CGTP
[[Page 11547]]
(Sec. 1271.1(b)). Section 1271.155(a) permits the submission of a
request for FDA approval of an exemption from or alternative to any
requirement in subpart C or D of part 1271. Section 1271.290(c)
requires such establishments to affix a distinct identification code to
each HCT[sol]P that it manufactures that relates the HCT[sol]P to the
donor and to all records pertaining to the HCT[sol]P. Whenever an
establishment distributes an HCT[sol]P to a consignee, Sec.
1271.290(f) requires the establishment to inform the consignee, in
writing, of the product tracking requirements and the methods the
establishment uses to fulfill the requirements. Non-reproductive
HCT[sol]P establishments described in Sec. 1271.10 are required under
Sec. Sec. 1271.350(a)(1) and (a)(3) to investigate and report to FDA
adverse reactions (defined in Sec. 1271.3(y)) using Form FDA-3500A
(Sec. 1271.350(a)(2)). Form FDA-3500A is approved under OMB Control
No. 0910-0291. Section 1271.370(b) and (c) requires establishments to
include specific information either on the HCT[sol]P label or with the
HCT[sol]P.
The standard operating procedures (SOP) provisions under part 1271
include the following: (1) Section 1271.160(b)(2) (receiving,
investigation, evaluating, and documenting information relating to core
CGTP requirements, including complaints, and for sharing information
with consignees and other establishments); (2) Sec. 1271.180(a) (to
meet core CGTP requirements for all steps performed in the manufacture
of HCT[sol]Ps); (3) Sec. 1271.190(d)(1) (facility cleaning and
sanitization); (4) Sec. 1271.200(b) (cleaning, sanitizing, and
maintenance of equipment); (5) Sec. 1271.200(c) (calibration of
equipment); (6) Sec. 1271.230(a) and (c) (validation of changes to a
process); (7) Sec. 1271.250(a) (controls for labeling HCT[sol]Ps); (8)
Sec. 1271.265(e) (receipt, predistribution shipment, availability for
distribution, and packaging and shipping of HCT[sol]Ps); (9) Sec.
1271.265(f) (suitable for return to inventory); (10) Sec. 1271.270(b)
(records management system); (11) Sec. 1271.290(b)(1) (system of
HCT[sol]P tracking); and (12) Sec. 1271.320(a) (review, evaluation,
and documentation of complaints (as defined in Sec. 1271.3(aa))).
Section 1271.155(f) requires an establishment operating under the
terms of an exemption or alternative to maintain documentation of the
terms and date of FDA approval. Section 1271.160(b)(3) requires
documentation of appropriate corrective actions taken as a result of an
audit of the quality program. Section 1271.160(b)(6) requires
documentation of HCT[sol]P deviations. Section 1271.160(d) requires
documentation of computer validation or verification activities and
results when computers are used to comply with the core CGTP
requirements for its intended use. Section 1271.190(d)(2) requires
documentation of all facility cleaning and sanitation activities
performed to prevent contamination of HCT[sol]Ps. Section 1271.195(d)
requires documentation of environmental control and monitoring
activities. Section 1271.200(e) requires documentation of equipment
maintenance, cleaning, sanitizing, calibration, and other activities.
Section 1271.210(d) requires documentation of the receipt,
verification, and use of each supply or reagent. Section 1271.230(a)
requires documentation of validation activities when the results of a
process cannot be fully verified by subsequent inspection and tests.
Section 1271.230(c) requires documentation of the review and evaluation
of a process and revalidation of the process, if necessary, when any
changes to a validated process occur. Section 1271.260(d) and (e)
requires documentation of any corrective action taken when proper
storage conditions are not met and documentation of storage
temperatures for HCT[sol]Ps. Section 1271.265(c)(1) requires
documentation that release criteria have been met before distribution
of an HCT[sol]P. Section 1271.265(c)(3) requires documentation of any
departure from a procedure at the time of its occurrence. Section
1271.265(e) requires documentation of the receipt, predistribution
shipment, distribution, and packaging and shipping of HCT[sol]Ps.
Section 1271.270(a) requires documentation of each step in
manufacturing required in part 1271, subparts C and D. Section
1271.270(e) requires documentation of the name and address, and a list
of responsibilities of any establishment that performs a manufacturing
step for an establishment. Sections 1271.290(d) and (e) require
documentation of a method for recording the distinct identification
code and type of each HCT[sol]P distributed to a consignee to enable
tracking from the consignee to the donor and to enable tracking from
the donor to the consignee or final disposition. Section 1271.320(b)
requires an establishment to maintain a record of each complaint that
it receives, that contains relevant information for proper review and
evaluation.
Respondents to this information collection are establishments that
recover, process, store, label, package, or distribute any HCT[sol]P,
or perform donor screening or testing. The estimates provided below are
based on the most recent available information from FDA's database
system and trade organizations. The hours per response and hours per
record are based on data provided by the Eastern Research Group, or FDA
experience with similar recordkeeping or reporting requirements.
There are an estimated 2,281 HCT[sol]P establishments (conventional
tissue, eye tissue, peripheral blood stem cell, stem cell products from
cord blood, reproductive tissue, and sperm banks), including 692
manufacturers of HCT[sol]P products regulated under the Federal Food,
Drug, and Cosmetics Act and section 351 of the PHS Act (42 U.S.C. 262),
that have registered and listed with FDA. In addition, we estimate that
251 new establishments have registered with FDA (Sec. 1271.10(b)(1)
and (b)(2) and Sec. 1271.25(a) and (b)). There are an estimated 2,230
listing updates (Sec. Sec. 1271.10(b)(2), 1271.21(c)(ii), and
1271.25(c)) and 565 location/ownership amendments (Sec. 1271.26).
Under Sec. 1271.55(a), an estimated total of 2,167,396 HCT[sol]Ps
(which include conventional tissues, eye tissues, hematopoetic stem
cells/progenitor cells, and reproductive cells and tissues) and an
estimated total of 2,026,024 non-reproductive cells and tissues (total
HCT[sol]Ps minus reproductive cells and tissues) are distributed per
year by an estimated 1,589 establishments (2,281 - 692 = 1,589
establishments with approved applications).
Under Sec. 1271.60(c) and (d)(2), FDA estimates that 1,375
establishments shipped an estimated 286,000 HCT[sol]Ps under
quarantine, and that an estimated 18 establishments requested an
exemption from or alternative to any requirement under part 1271,
subpart C or D, specifically under Sec. 1271.155(a).
Under Sec. 1271.290(c) and Sec. 1271.370(b) and (c), an estimated
1,694 non-reproductive HCT[sol]P establishments label each of their
2,026,024 HCT[sol]Ps with certain information. These establishments are
also required to inform their consignees in writing of the requirements
for tracking and of their established tracking system under Sec.
1271.290(f).
FDA estimates 38 HCT[sol]P establishments submitted 76 adverse
reaction reports involving a communicable disease (Sec.
1271.350(a)(1)).
FDA estimates that 251 new establishments will create SOPs, and
that 2,281 establishments will review and revise existing SOPs
annually.
FDA estimates that 1,141 HCT[sol]P establishments (2,281 x 50% =
1,141)
[[Page 11548]]
and 847 non-reproductive HCT[sol]P establishments (1,694 x 50% = 847)
record and justify a departure from the procedures (Sec. Sec.
1271.47(d) and 1271.265(c)(3)).
Under Sec. 1271.50(a), HCT[sol]P establishments are required to
have a documented medical history interview about the donor's medical
history and relevant social behavior as part of the donor's relevant
medical records for each of the estimated total of 91,240 donors (which
include conventional tissue donors, eye tissue donors, peripheral and
cord blood stem cell donors, and reproductive cell and tissue donors),
and the estimated total of 86,394 non-reproductive cells and tissue
donors (total donors minus reproductive cell and tissue donors).
FDA estimates that 684 HCT[sol]P establishments (2,281 x 30% = 684)
document an urgent medical need for an HCT[sol]P and notify the
physician using the HCT[sol]P (Sec. 1271.60(d)(3) and (d)(4) and Sec.
1271.65(b)(3)(iii)).
FDA also estimates that 1,824 HCT[sol]P establishments (2,281 x 80%
= 1,824) have to maintain records for an average of 2 contract
establishments that perform a manufacturing process step for them
(Sec. 1271.270(e)) and 1,141 HCT[sol]P establishments maintain an
average of 5 complaint records annually (Sec. 1271.320(b)).
In some cases, the estimated burden may appear to be lower or
higher than the burden experienced by individual establishments. The
estimated burden in these charts is an estimated average burden, taking
into account the range of impact each regulation may have.
FDA estimates the burden of this collection of information as
follows:
Table 1.--Estimated Annual Reporting Burden\1\
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No. of Annual Frequency Total Annual Hours per
21 CFR Section Respondents per Response Responses Response Total Hours
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1271.10(b)(1) and 1271.21(b)\2\ 2,281 1 2,281 .5 1,141
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1271.10(b)(1) and (b)(2), 1271.21(a), and 1271.25(a) 251 1 251 .75 188
and (b)\2\
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1271.10(b)(2), 1271.21(c)(2)(ii), and 1271.25(c)\2\ 2,230 1 2,230 .5 1,115
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1271.26\2\ 565 1 565 .25 141
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1271.55(a) 1,589 1,364 2,167,396 .5 1,083,698
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1271.60(c) and (d)(2) 1,375 208 286,000 .5 143,000
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1271.155(a) 18 1 18 3 54
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1271.290(c) 1,694 1,196 2,026,024 .083 168,835
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1271.290(f) 1,694 1 1,694 1 1,694
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1271.350(a)(1) and (a)(3) 38 2 76 1 76
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1271.370(b) and (c) 1,694 1,196 2,026,024 .25 506,506
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Total 1,906,448
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Using Form FDA 3356.
Table 2.--Estimated Annual Recordkeeping Burden\1\
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No. of Annual Frequency Total Annual
21 CFR Section Recordkeepers per Recordkeeping Records Hours per Record Total Hours
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New SOPs\2\ 251 1 251 48 12,048
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SOP Update\2\ 2,281 1 2,281 24 54,744
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1271.47(d) 1,141 1 1,141 1 1,141
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1271.50(a) 2,281 40 91,240 5 456,200
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1271.55(d)(1) 2,281 40 91,240 1 91,240
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1271.55(d)(2) 2,281 1 2,281 1 2,281
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1271.55(d)(4) 2,281 1 2,281 120 273,720
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1271.60(d)(3) and (d)(4), and 1271.65(b)(3)(iii) 684 1 684 2 1,368
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1271.155(f) 18 1 18 .25 5
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1271.160(b)(3) and (b)(6) 1,694 12 20,328 1 20,328
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1271.160(d) 1,694 12 20,328 1 20,328
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1271.190(d)(2) 1,694 12 20,328 1 20,328
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1271.195(d) 1,694 12 20,328 1 20,328
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1271.200(e) 1,694 12 20,328 1 20,328
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1271.210(d) 1,694 12 20,328 1 20,328
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1271.230(a) 1,694 12 20,328 1 20,328
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1271.230(c) 1,694 1 1,694 1 1,694
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1271.260(d) 1,694 12 20,328 .25 5,082
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1271.260(e) 1,694 365 618,310 .083 51,526
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1271.265(c)(1) 1,694 1,196 2,026,024 .083 168,835
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1271.265(c)(3) 847 1 847 1 847
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1271.265(e) 1,694 1,196 2,026,024 .083 168,835
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1271.270(a) 1,694 1,196 2,026,024 .25 506,506
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1271.270(e) 1,824 2 3,648 .5 1,824
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1271.290(d) and (e) 1,694 51 86,394 .25 21,599
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1271.320(b) 1,141 5 5,705 1 5,705
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Total 1,967,496
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Sections 1271.47(a), 1271.85(b)(2), 1271.160(b)(2) and (d)(1), 1271.180(a), 1271.190(d)(1), 1271.200(b), 1271.200(c), 1271.230(a), 1271.250(a), and
1271.265(e).
Dated: March 8, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-5229 Filed 3-10-10; 8:45 am]
BILLING CODE 4160-01-S