[Federal Register Volume 72, Number 17 (Friday, January 26, 2007)]
[Notices]
[Pages 3858-3862]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-1196]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0018]


Agency Information Collection Activities; Proposed Collection; 
Comment Request; Human Cells, Tissues, and Cellular and Tissue-Based 
Products: Establishment Registration and Listing; Form Food and Drug 
Administration 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/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 March 27, 2007.

ADDRESSES:  Submit electronic comments on the collection of information 
to: http://www.fda.gov/dockets/ecomments. Submit written comments on 
the collection of information to the Division of Dockets

[[Page 3859]]

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:  Jonna Capezzuto, Office of the Chief 
Information Officer (HFA-250), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal 
agencies must obtain approval from the Office of Management and Budget 
(OMB) for each collection of information they conduct or sponsor. 
``Collection of information'' is defined in 44 U.S.C. 3502(3) and 5 CFR 
1320.3(c) and includes agency requests or requirements that members of 
the public submit reports, keep records, or provide information to a 
third party. Section 3506(c)(2)(A) of the PRA (44 U.S.C. 3506(c)(2)(A)) 
requires Federal agencies to provide a 60-day notice in the Federal 
Register concerning each proposed collection of information, including 
each proposed extension of an existing collection of information, 
before submitting the collection to OMB for approval. To comply with 
this requirement, FDA is publishing notice of the proposed collection 
of information set forth in this document.
    With respect to the following collection of information, FDA 
invites comments on these topics: (1) Whether the proposed collection 
of information is necessary for the proper performance of FDA's 
functions, including whether the information will have practical 
utility; (2) the accuracy of FDA's estimate of the burden of the 
proposed collection of information, including the validity of the 
methodology and assumptions used; (3) ways to enhance the quality, 
utility, and clarity of the information to be collected; and (4) ways 
to minimize the burden of the collection of information on respondents, 
including through the use of automated collection techniques, when 
appropriate, and other forms of information technology.

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--21 CFR Part 
1271 (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/Ps pose some 
risk of carrying pathogens that could potentially infect recipients or 
handlers. FDA has issued regulations related to HCT/Ps involving 
establishment registration and listing using Form FDA 3356; eligibility 
determination for donors; and CGTP.
    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 any HCT/Ps, 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/P manufactured (Sec.  1271.10(b)(2)). 
Section 1271.21(a) requires the initial establishment registration, and 
Sec.  1271.25(a) and (b) identifies the required initial registration 
and HCT/P listing information. Section 1271.21(b) requires an annual 
update of the establishment registration. Section 1271.21(c)(ii) 
requires establishments to submit HCT/P listing updates when an HCT/P 
is changed as described in Sec.  1271.25(c). Section 1271.25(c) 
identifies the required HCT/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 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/cber/tissue/tisreg.htm).
    Eligibility Determination for Donors
    FDA requires HCT/P establishments described in Sec.  1271.1(b) to 
screen and test the donors of cells and tissue used in those products 
for risk factors for and clinical evidence of relevant communicable 
diseases agents and diseases. The documented determination of a donor's 
eligibility is made by a responsible person 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)). 
HCT/P establishments are permitted to ship an HCT/P only if it is 
accompanied by documentation of the donor-eligibility determination 
(Sec.  1271.55(a)). This requirement applies to an HCT/P from a donor 
determined to be eligible as well as to a product from a donor who is 
determined to be ineligible and made available for use under certain 
provisions. The accompanying documentation must contain a summary of 
records used to determine donor eligibility, and a statement whether, 
based on the results of the screening and testing of the donor, that 
the donor is determined to be eligible or ineligible.
    Records used in determining the eligibility of a donor, i.e., 
results and interpretations of screening and testing, the donor 
eligibility determination, the name and address of the testing 
laboratory or laboratories, and the name of the responsible person who 
made the determination and the date, must be maintained (Sec.  
1271.55(d)(1)). If any information on the donor is not in English, the 
HCT/P establishment must retain the original record and the statement 
of authenticity from the translator (Sec.  1271.55(d)(2)). HCT/P 
establishments must retain the records pertaining to HCT/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, before completion of 
screening and testing, the HCT/P establishment must provide the donor 
identification, a statement that the donor-eligibility determination is 
not completed and that the product is not to be used until eligibility 
determination is completed (Sec.  1271.60(c)). With the use of a 
product from an incompletely tested donor, the results of any completed 
donor screening and testing, and a list of any required screening and 
testing not yet completed must accompany the HCT/P (Sec.  
1271.60(d)(2)). When using an HCT/P from an ineligible donor, 
documentation by the HCT/P establishment is required showing that the 
recipient's physician received notification of the screening and 
testing results (Sec.  Sec.  1271.60(d)(3) and 1271.65(b)(3)).
    An HCT/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 
positive for cytomegalovirus (Sec.  1271.85(b)(2)). The HCT/P 
establishment must record any departure from the procedures (Sec.  
1271.47(d)).
    Current Good Tissue Practice
    FDA requires certain HCT/P establishments to follow CGTPs. Section 
1271.155(a) permits the submission of a request for FDA approval of an 
exemption or an alternative from any requirement in subpart C or D of 
part

[[Page 3860]]

1271. Section 1271.290(c) requires the establishment to affix a 
distinct identification code to each HCT/P relating the HCT/P to the 
donor and all records pertaining to the HCT/P. Whenever an 
establishment initially distributes an HCT/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/P 
establishments described in Sec.  1271.10 are required under Sec.  
1271.350(a)(1) and (b)(1) to report to FDA adverse reactions (defined 
in Sec.  1271.3(y)) and HCT/P deviations (defined in Sec.  1271.3(dd)). 
Section 1271.370(b) and (c) requires establishments to include specific 
information either on the HCT/P label or in the package insert.
    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 received from other sources and for sharing 
information with consignees and other establishments); (2) section 
1271.180(a) (to meet core CGTP requirements for all steps performed in 
the manufacture of HCT/Ps); (3) section 1271.190(d)(1) (facility 
cleaning and sanitization); (4) section 1271.200(b) (cleaning, 
sanitizing, and maintenance of equipment); (5) section 1271.200(c) 
(calibration of equipment); (6) section 1271.230(a) (verification or 
validation of changes to a process); (7) section 1271.250(a) (controls 
for labeling HCT/Ps); (8) section 1271.265(e) (receipt, pre-
distribution shipment, availability for distribution, and packaging and 
shipping of HCT/Ps); (9) section 1271.265(f) (suitable for return to 
inventory); (10) section 1271.270(b) (records management system); (11) 
section 1271.290(b)(1) (system of HCT/P tracking); and (12) section 
1271.320(a) (review, evaluation, and documentation of all complaints).
    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 corrective actions taken as a result of an audit of 
the quality program. Section 1271.160(b)(6) requires documentation of 
HCT/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 
significant facility cleaning and sanitation. Section 1271.195(d) 
requires documentation of environmental control and monitoring 
activities. Section 1271.200(e) requires documentation of all 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 the storage temperature of HCT/Ps and any 
corrective action taken when acceptable storage conditions are not met. 
Section 1271.265(c)(1) requires documentation that all release criteria 
are met before distribution of an HCT/P. Section 1271.265(c)(3) 
requires documentation of any departure from a procedure at the time of 
occurrence. Section 1271.265(e) requires documentation of the receipt, 
pre-distribution shipment, distribution, and packaging and shipping of 
HCT/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 you. Section 1271.290(d) and (e) requires documentation of the 
disposition of each non-reproductive HCT/P as part of its tracking 
method. Section 1271.320(b) requires an establishment to maintain a 
record of each complaint that it receives, including a review and 
evaluation.
    Respondents to this information collection are establishments that 
recover, process, store, label, package or distribute any HCT/P, or 
perform donor screening or testing. The estimates provided below are 
based on information from FDA's database system and trade organizations 
for 2006. 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 2,017 HCT/P (conventional tissue, eye 
tissue, peripheral blood stem cell, stem cell products from cord blood, 
reproductive tissue, and sperm banks) establishments, including 481 
manufacturers of HCT/P products regulated under the Federal Food, Drug, 
and Cosmetics Act and section 351 of the PHS Act, that have registered 
and listed with FDA. In addition, we estimate that 241 new 
establishments have registered with FDA (Sec. Sec.  1271.10(b)(1) and 
(b)(2) and 1271.25(a) and (b)). There are an estimated 3,289 listing 
updates (Sec. Sec.  1271.10(b)(2), 1271.21(c)(2)(ii) and 1271.25(c)) 
and 500 location/ownership amendments (Sec.  1271.26).
    Under Sec.  1271.55(a), an estimated 1,677,105 HCT/Ps 
(approximately 1,500,000 conventional tissues, 44,186 eye tissues, 
7,919 hematopoetic stem cells/progenitor cells (total of 1,552,105 non-
reproductive cells and tissues), and 125,000 reproductive cells and 
tissues) are distributed per year by an estimated 1,536 establishments 
(2,017 - 481 establishments with approved applications).
    Under Sec.  1271.60(c), FDA estimates that 1,200 establishments 
shipped an estimated 250,000 HCT/P under quarantine, and that an 
estimated 8 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. Sec.  1271.290(c) and 1271.370(b) and (c), the estimated 
1,449 non-reproductive HCT/P establishments label each of their 
1,552,105 HCT/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 42 HCT/P establishments submitted 67 adverse reaction 
reports involving communicable disease (Sec.  1271.350(a)(1)), and 81 
establishments submitted 144 deviation reports relating to the core 
CGTP requirements (Sec.  1271.350(b)(1)).
    FDA estimates that 241 new establishments will create SOPs, and 
that 2,017 establishments will review and revise existing SOPs 
annually.
    FDA estimates that 1,009 HCT/P establishments (2,017x50%=1,009) and 
725 non-reproductive HCT/P establishments (1,449x50%=725) record and 
justify a departure from the procedures (Sec.  1271.47(d) and Sec.  
1271.265(c)(3)).
    Under Sec.  1271.50(a), HCT/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 77,944 donors

[[Page 3861]]

(approximately 23,295 conventional tissue donors, 42,649 eye tissue 
donors, 7,000 peripheral and cord blood stem cell donors (72,944 non-
reproductive cells and tissue donors), and 5,000 reproductive cell and 
tissue donors).
    FDA estimates that 605 HCT/P establishments (2,017x30%=605) 
document an urgent medical need of the product to notify the physician 
using the HCT/P (Sec. Sec.  1271.60(d)(3) and 1271.65(b)(3)).
    FDA also estimates that 1614 HCT/P establishments (2,017x80%=1,614) 
have to maintain records for an average of 2 contract establishments to 
perform their manufacturing process (Sec.  1271.270(e)) and 1,009 HCT/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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                                      Annual Frequency per     Total Annual        Hours per
 21 CFR Section  No. of Respondents         Response             Responses          Response       Total Hours
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1271.10(b)(1)                2,017                      1               2,017              0.5          1,008.5
 and
 1271.21(b)\2\
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1271.10(b)(1)                  241                      1                 241             0.75           180.75
 and (b)(2),
 1271.21(a),
 and 1271.25(a)
 and (b)\2\
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1271.10(b)(2),               3,289                      1               3,289              0.5         1,644.50
 1271.21(c)(2)(
 ii) and
 1271.25(c)\2\
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1271.26\2\                     500                      1                 500             0.25              125
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1271.55(a)                   1,536               1,091.87           1,677,105              0.5       838,552.50
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1271.60(c) and               1,200                 208.33             250,000              0.5          125,000
 (d)(2)
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1271.155(a)                      8                      1                   8                3               24
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1271.290(c)                  1,449               1,071.16           1,552,105             0.08        124,168.4
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1271.290(f)                  1,449                      1               1,449                1            1,449
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1271.350(a)(1)                  42                   1.60                  67                1               67
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1271.350(b)(1)                  81                   1.78                 144                1              144
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1271.370(b) and              1,449               1,071.16           1,552,105             0.25       388,026.25
 (c)
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Total            ..................  .....................  ..................  ...............    1,480,389.80
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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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                                                             Annual Frequency per
           21 CFR Section             No. of Recordkeepers      Recordkeeping         Total Annual Records        Hours per Record        Total Hours
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New SOPs\2\                                           241                      1                         241                     48              11,568
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SOP Update\2\                                       2,017                      1                       2,017                     24              48,408
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1271.47(d)                                          1,009                      1                       1,009                      1               1,009
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1271.50(a)                                          2,017                  38.64                      77,944                      5             389,720
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1271.55(d)(1)                                       2,017                  38.64                      77,944                      1              77,944
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1271.55(d)(2)                                       2,017                      1                       2,017                      1               2,017
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1271.55(d)(4)                                       2,017                      1                       2,017                    120             242,040
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1271.60(d)(3) and 1271.65(b)(3)                       605                      1                         605                      2               1,210
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1271.155(f)                                             8                      1                           8                   0.25                   2
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1271.160(b)                                         1,449                     12                      17,388                      1              17,388
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1271.160(d)                                         1,449                     12                      17,388                      1              17,388
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1271.190(d)(2)                                      1,449                     12                      17,388                      1              17,388
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[[Page 3862]]

 
1271.195(d)                                         1,449                     12                      17,388                      1              17,388
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1271.200(e)                                         1,449                     12                      17,388                      1              17,388
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1271.210(d)                                         1,449                     12                      17,388                      1              17,388
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1271.230(a)                                         1,449                     12                      17,388                      1              17,388
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1271.230(c)                                         1,449                      1                       1,449                      1               1,449
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1271.260(d)                                         1,449                     12                      17,388                   0.25               4,347
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1271.260(e)                                         1,449                    365                     528,885                   0.08            42,310.8
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1271.265(c)(1)                                      1,449               1,071.16                   1,552,105                   0.08           124,168.4
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1271.265(c)(3)                                        725                      1                         725                      1                 725
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1271.265(e)                                         1,449               1,071.16                   1,552,105                   0.08           124,168.4
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1271.270(a)                                         1,449               1,071.16                   1,552,105                   0.25          388,026.25
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1271.270(e)                                          1614                      2                        3228                    0.5               1,614
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1271.290(d) and (e)                                 1,449                  50.34                      72,944                   0.25              18,236
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1271.320(b)                                         1,009                      5                       5,045                      1               5,045
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Total                                .....................  .....................  ..........................  .....................       1,605,723.85
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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), 1271.180(a), 1271.190(d)(1), 1271.20c(b) and (c), 1271.230(a), 1271.250(a), and 1271.265(e).


    Dated: January 19, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-1196 Filed 1-25-07; 8:45 am]
BILLING CODE 4160-01-S