[Federal Register Volume 79, Number 15 (Thursday, January 23, 2014)]
[Notices]
[Pages 3822-3825]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-01223]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2013-N-0731]


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 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 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 
February 24, 2014.

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 0910-0543. 
Also include the FDA docket number found in brackets in the heading of 
this document.

FOR FURTHER INFORMATION CONTACT: FDA PRA Staff, Office of Operations, 
Food and Drug Administration, 1350 Piccard Dr., PI50-400B, Rockville, 
MD 20850, [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.

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 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 an HCT/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/P 
manufactured (Sec.  1271.10(b)(2)). Section 1271.21(a) requires an 
establishment to follow certain procedures for initial registration and 
listing of HCT/Ps, and Sec.  1271.25(a) and (b) identifies the required 
initial registration and HCT/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/P listing 
updates if a change as described in Sec.  1271.25(c) has occurred. 
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 (HCT/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 at (http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/EstablishmentRegistration/TissueEstablishmentRegistration/default.htm).

Eligibility Determination for Donors

    In brief, FDA requires certain HCT/P establishments described in 
Sec.  1271.1(b) to determine donor eligibility based on donor screening 
and testing for relevant communicable disease agents and diseases 
except as provided under Sec.  1271.90. The documented determination of 
a donor's eligibility is made by a responsible person as 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/P once the donor-eligibility determination has been 
made (Sec.  1271.55(a)). This requirement applies both to an HCT/P from 
a donor who is determined to be eligible as well as to an HCT/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, as defined in Sec.  1271.3(u) (Sec.  1271.60). Once the donor-
eligibility determination has been made, the HCT/P must be accompanied 
by a summary of records used to make the donor-eligibility 
determination (Sec.  1271.55(b)), and a statement whether,

[[Page 3823]]

based on the results of the screening and testing of the donor, 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 maintained and translated to 
English, and accompanied by a statement of authenticity by the 
translator (Sec.  1271.55(d)(2)). HCT/P establishments must retain the 
records pertaining to a particular HCT/P at least 10 years after the 
date of its administration, or, if the date of administration is not 
known, then at least 10 years after the date of the HCT/P's 
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/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 implanted, transplanted, infused, or transferred 
until completion of the donor-eligibility determination, except in 
cases of urgent medical need, as defined in Sec.  1271.3(u) (Sec.  
1271.60(c)). When an HCT/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 that has not yet been 
completed also must accompany the HCT/P (Sec.  1271.60(d)(2)). When an 
HCT/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/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. Sec.  1271.60(d)(3) and (d)(4), 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 of 
viable, leukocyte-rich cells or tissue testing reactive for 
cytomegalovirus (Sec.  1271.85(b)(2)). The HCT/P establishment must 
record and justify any departure from a procedure relevant to 
preventing risks of communicable disease transmission at the time of 
its occurrence (Sec.  1271.47(d)).

Current Good Tissue Practice (CGTP)

    FDA requires HCT/P establishments to follow CGTP (Sec.  1271.1(b)). 
Section 1271.155(a) permits the submission of a request for FDA 
approval of an exemption from or an alternative to any requirement in 
subpart C or D of part 1271. Section 1271.290(c) requires 
establishments to affix a distinct identification code to each HCT/P 
that they manufacture that relates the HCT/P to the donor and to all 
records pertaining to the HCT/P. Whenever an establishment 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 these 
requirements. Non-reproductive HCT/P establishments described in Sec.  
1271.10 are required under 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 number 0910-0291. Section 1271.370(b) and 
(c) requires establishments to include specific information either on 
the HCT/P label or with the HCT/P.
    The standard operating procedures (SOPs) provisions under part 1271 
include the following: (1) Section 1271.160(b)(2) (receiving, 
investigating, 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/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 a process and 
review and evaluation of changes to a validated process); (7) Sec.  
1271.250(a) (controls for labeling HCT/Ps); (8) Sec.  1271.265(e) 
(receipt, predistribution shipment, availability for distribution, and 
packaging and shipping of HCT/Ps); (9) Sec.  1271.265(f) (suitable for 
return to inventory); (10) Sec.  1271.270(b) and (d) (records 
management system); (11) Sec.  1271.290(b)(1) (system of HCT/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 FDA's 
grant of the exemption or approval and the date on which it began 
operating under the terms of the exemption or alternative. Section 
1271.160(b)(3) requires the quality program of an establishment that 
performs any step in the manufacture of HCT/Ps to document corrective 
actions relating to core CGTP requirements. Section 1271.160(b)(6) 
requires documentation of HCT/P deviations. Section 1271.160(d) 
requires, in brief, documentation of validation of computer software if 
the establishment relies upon it to comply with core CGTP requirements. 
Section 1271.190(d)(2) requires documentation of all cleaning and 
sanitation activities performed to prevent contamination of HCT/Ps. 
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, in brief, documentation of 
the receipt, verification, and use of each supply or reagent. Section 
1271.230(a) requires documentation of validation activities and results 
when the results of processing described in Sec.  1271.220 cannot be 
fully verified by subsequent inspection and tests. Section 1271.230(c) 
requires that when changes to a validated process subject to Sec.  
1271.230(a) occur, documentation of the review and evaluation of the 
process and revalidation, if necessary, must occur. Section 1271.260(d) 
and (e) requires documentation of any corrective action taken when 
proper storage conditions are not met and documentation of the storage 
temperature for HCT/Ps. Section 1271.265(c)(1) requires documentation 
that all release criteria have been met before distribution of an HCT/
P. Section 1271.265(c)(3) requires documentation of any departure from 
a procedure relevant to preventing risks of communicable disease 
transmission at the time of occurrence. Section 1271.265(e) requires 
documentation of the activities in paragraphs (a) through (d) of this 
section, which must include identification of the HCT/P and the 
establishment that supplied the HCT/P, activities performed and the 
results of each activity, date(s) of activity, quantity of HCT/P 
subject to the

[[Page 3824]]

activity, and disposition of the HCT/P. 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) require documentation of a method for recording the 
distinct identification code and type of each HCT/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. The complaint file must contain 
sufficient information about each complaint for proper review and 
evaluation of the complaint and for determining whether the complaint 
is an isolated event or represents a trend.
    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 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 2,706 HCT/P establishments (conventional 
tissue, eye tissue, peripheral blood stem cell, stem cell products from 
cord blood, reproductive tissue, and sperm banks), including 741 
manufacturers of HCT/P products regulated under the Federal Food, Drug, 
and Cosmetic 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 218 
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 3,737 
listing updates (Sec. Sec.  1271.10(b)(2), 1271.21(c)(ii), and 
1271.25(c)) and 1,222 location/ownership amendments (Sec.  1271.26).
    Under Sec.  1271.55(a), an estimated total of 2,167, 396 HCT/Ps 
(which include conventional tissues, eye tissues, hematopoetic stem 
cells/progenitor cells, and reproductive cells and tissues), and an 
estimated total of 2,026,861 non-reproductive cells and tissues (total 
HCT/Ps minus reproductive cells and tissues) are distributed per year 
by an estimated 1,965 establishments (2,706-741 = 1,965) with approved 
applications.
    Under Sec.  1271.60(c) and (d)(2), FDA estimates that 1,375 
establishments shipped an estimated 286,000 HCT/Ps under quarantine, 
and that an estimated 26 establishments requested 40 exemptions 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 
1,694 non-reproductive HCT/P establishments label each of their 
2,026,861 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 24 HCT/P establishments submitted 206 adverse 
reaction reports with 167 involving a communicable disease (Sec.  
1271.350(a)(1)).
    FDA estimates that 218 new establishments will create SOPs, and 
that 2,706 establishments will review and revise existing SOPs 
annually.
    FDA estimates that 1,353 HCT/P establishments (2,706 x 50 percent = 
1,353) and 847 non-reproductive HCT/P establishments (1,694 x 50 
percent = 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/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 91,756 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 86,156 non-reproductive cells and tissue donors 
(total donors minus reproductive cell and tissue donors).
    FDA estimates that 812 HCT/P establishments (2,706 x 30 percent = 
812) 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 2,165 HCT/P establishments (2,706 x 80 
percent = 2,165) have to maintain records for an average of 2 contract 
establishments to perform their manufacturing process (Sec.  
1271.270(e) and 1,353 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 July 12, 2013 (78 FR 41934), FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                 Number of
               21 CFR section                    Number of     responses per   Total annual           Average burden per response           Total hours
                                                respondents     respondent       responses
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1271.10(b)(1) and 1271.21(b) \2\............           2,706            1              2,706  .5 (30 minutes)...........................           1,353
1271.10(b)(1) and (b)(2), 1271.21(a), and                218            1                218  .75 (45 minutes)..........................             164
 1271.25(a) and (b) \2\.
1271.10(b)(2), 1271.21(c)(ii), and                     3,737            1              3,737  .5 (30 minutes)...........................           1,869
 1271.25(c) \2\.
1271.26 \2\.................................           1,222            1              1,222  .25 (15 minutes)..........................             306
1271.155(a).................................              26            1.54              40  3.........................................             120
1271.350(a)(1) and (a)(3)...................              24            8.58             206  1.........................................             206
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................           4,018
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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.


[[Page 3825]]


                                                   Table 2--Estimated Annual Recordkeeping Burden \1\
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                                                                 Number of
               21 CFR section                    Number of      records per    Total annual        Average burden per recordkeeping         Total hours
                                               recordkeepers   recordkeeper       records
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New SOPs \2\................................             218            1                218  48........................................          10,464
SOP Update \2\..............................           2,706            1              2,706  24........................................          64,944
1271.47(d)..................................           1,353            1              1,353  1.........................................           1,353
1271.50(a)..................................           2,706           33.91          91,756  5.........................................         458,780
1271.55(d)(1)...............................           2,706           33.91          91,756  1.........................................          91,756
1271.55(d)(2)...............................           2,706            1              2,706  1.........................................           2,706
1271.55(d)(4)...............................           2,706            1              2,706  120.......................................         324,720
1271.60(d)(3) and (d)(4) 1271.65(b)(3)......             812            1                812  2.........................................           1,624
1271.155(f).................................              26            1.54              40  .25 (15 minutes)..........................              10
1271.160(b)(3) and (b)(6)...................           1,694           12             20,328  1.........................................          20,328
1271.160(d).................................           1,694           12             20,328  1.........................................          20,328
1271.190(d)(2)..............................           1,694           12             20,328  1.........................................          20,328
1271.195(d).................................           1,694           12             20,328  1.........................................          20,328
1271.200(e).................................           1,694           12             20,328  1.........................................          20,328
1271.210(d).................................           1,694           12             20,328  1.........................................          20,328
1271.230(a).................................           1,694           12             20,328  1.........................................          20,328
1271.230(c).................................           1,694            1              1,694  1.........................................           1,694
1271.260(d).................................           1,694           12             20,328  .25 (15 minutes)..........................           5,082
1271.260(e).................................           1,694          365            618,310  .083 (5 minutes)..........................          51,320
1271.265(c)(1)..............................           1,694        1,196.49       2,026,861  .083 (5 minutes)..........................         168,229
1271.265(c)(3)..............................             847            1                847  1.........................................             847
1271.265(e).................................           1,694        1,196.49       2,026,861  .083 (5 minutes)..........................         168,229
1271.270(a).................................           1,694        1,196.49       2,026,861  .25 (15 minutes)..........................         506,715
1271.270(e).................................           2,165            2              4,330  .5 (30 minutes)...........................           2,165
1271.290(d) and (e).........................           1,694           50.86          86,156  .25 (15 minutes)..........................          21,539
1271.320(b).................................           1,353            5              6,765  1.........................................           6,765
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................       2,031,238
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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) and (c),
  1271.250(a), 1271.265(e) and (f), 1271.270(b) and (d), 1271.290(b)(1), and 1271.320(a).


                                               Table 3--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                 Number of
                                                 Number of      disclosures    Total annual
               21 CFR section                   respondents         per         Disclosures          Average burden per disclosure          Total hours
                                                                respondent
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.55(a)..................................           1,965        1,103          2,167,396  .5 (30 minutes)...........................       1,083,698
1271.60(c) and (d)(2).......................           1,375          208            286,000  .5 (30 minutes)...........................         143,000
1271.290(c).................................           1,694        1,196.49       2,026,861  .083 (5 minutes)..........................         168,229
1271.290(f).................................           1,694            1              1,694  1.........................................           1,694
1271.370(b) and (c).........................           1,694        1,196.49       2,026,861  .25 (15 minutes)..........................         506,715
                                             -----------------------------------------------------------------------------------------------------------
    Total...................................  ..............  ..............  ..............  ..........................................       1,903,336
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.


    Dated: January 14, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-01223 Filed 1-22-14; 8:45 am]
BILLING CODE 4160-01-P