[Federal Register Volume 72, Number 81 (Friday, April 27, 2007)]
[Notices]
[Pages 21027-21030]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-8038]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2007N-0018]


Agency Information Collection Activities; Submission for Office 
of Management and Budget Review; 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 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 29, 
2007.

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: 202-395-6974. All comments should be identified with the OMB 
control number 0910-0543. Also include the FDA 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: In compliance with 44 U.S.C. 3507, FDA has 
submitted the following proposed collection of information to OMB for 
review and clearance.

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 (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 human cells, 
tissues, and cellular and tissue-based products (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 current good tissue practice (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

[[Page 21028]]

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 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) and (b)(2) to investigate and 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 any corrective action taken when acceptable 
storage conditions are not met and documentation of the storage 
temperature of HCT/Ps.
    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 the establishment. Section 1271.290(d) and (e) 
requires documentation of a method for the recording and disposition of 
each HCT/P as part of its tracking system. 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 Cosmetic 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

[[Page 21029]]

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 (2,017 x 50% = 1,009) 
and 725 non-reproductive HCT/P establishments (1,449 x 50% = 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 (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 (2,017 x 30% = 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 (2,017 x 80% = 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.
    In the Federal Register of January 26, 2007 (72 FR 3858), FDA 
published a 60-day notice requesting public comment on the information 
collection provisions. No comments were received.

                                 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              2,017                  1              2,017                0.5              1,009
 1271.21(b)(2)\2\
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1271.21(a), and                  241                  1                241               0.75                181
 1271.25(a) and
 (b)\2\
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1271.10(b)(2),                 3,289                  1              3,289                0.5              1,644
 1271.21(c)(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            838,553
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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         124,168.33
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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
 and (b)(2)
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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              .................  .................  .................  .................          1,480,390
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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.

    FDA estimates the burden of this collection of information as 
follows:

                               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\                      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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[[Page 21030]]

 
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                605                  1                605                  2              1,210
 1271.65(b)(3)
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1271.155(f)                        8                  1                  8               0.25                  2
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1271.160(b)(3)                 1,449                 12             17,388                  1             17,388
 and (b)(6)
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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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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         124,168.33
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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         124,168.33
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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)                    1,614                  2              3,228                0.5              1,614
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1271.290(d) and                1,449              50.34             72,944               0.25             18,236
 (e)
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1271.320(b)                    1,009                  5              5,045                  1              5,045
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Total              .................  .................  .................  .................        1,605,723.7
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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), 1271.200(b) and (c),
  1271.230(a), 1271.250(a), 1271.265(e), and 1271.320(a).


    Dated: April 20, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-8038 Filed 4-26-07; 8:45 am]
BILLING CODE 4160-01-S