
[Federal Register: July 9, 2010 (Volume 75, Number 131)]
[Notices]               
[Page 39537-39541]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09jy10-45]                         

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0101]

 
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.

-----------------------------------------------------------------------

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 August 
9, 2010.

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 e-mailed to oira_submission@omb.eop.gov. 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: Elizabeth Berbakos, Office of 
Information Management, Food and Drug Administration, 1350 Piccard Dr., 
PI50-400B, Rockville, MD 20850, 301-796-3792, 
Elizabeth.Berbakos@fda.hhs.gov.

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[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 current good tissue practice (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

[[Page 39538]]

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 (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.  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. Section 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),

[[Page 39539]]

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) 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.
    In the Federal Register of March 11, 2010 (75 FR 11545) FDA 
published a 60-day notice requesting public comment on the proposed 
collection of information. No comments were received on the information 
collection.
    FDA estimates the burden of this collection of information as 
follows:

                                                     Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               No. of         Annual Frequency       Total Annual        Hours per
                     21 CFR Section                         Respondents         per Response          Responses          Response         Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.10(b)(1) and 1271.21(b)\2\                                      2,281                     1              2,281               .5               1,141
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.10(b)(1) and (b)(2), 1271.21(a), and 1271.25(a)                   251                     1                251               .75                188
 and (b)\2\
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.10(b)(2), 1271.21(c)(2)(ii), and 1271.25(c)\2\                  2,230                     1              2,230               .50              1,115
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.26\2\                                                             565                     1                565               .25                141
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.55(a)                                                           1,589                 1,364          2,167,396               .50          1,083,698
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.60(c) and (d)(2)                                                1,375                   208            286,000               .50            143,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.155(a)                                                             18                     1                 18              3                    54
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.290(c)                                                          1,694                 1,196          2,026,024               .08            168,835
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.290(f)                                                          1,694                     1              1,694              1                 1,694
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.350(a)(1) and (a)(3)                                               38                     2                 76              1                    76
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.370(b) and (c)                                                  1,694                 1,196          2,026,024               .25            506,506
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                          1,906,448
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Using Form FDA 3356.


[[Page 39540]]


                                                   Table 2.--Estimated Annual Recordkeeping Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                              No. of         Annual Frequency       Total Annual
                    21 CFR Section                        Recordkeepers      per Recordkeeping        Records       Hours per  Record     Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
New SOPs\2\                                                           251                     1                251             48                 12,048
--------------------------------------------------------------------------------------------------------------------------------------------------------
SOP Update\2\                                                       2,281                     1              2,281             24                 54,744
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.47(d)                                                          1,141                     1              1,141              1                  1,141
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.50(a)                                                          2,281                    40             91,240              5                456,200
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.55(d)(1)                                                       2,281                    40             91,240              1                 91,240
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.55(d)(2)                                                       2,281                     1              2,281              1                  2,281
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.55(d)(4)                                                       2,281                     1              2,281            120                273,720
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.60(d)(3) and (d)(4), and 1271.65(b)(3)(iii)                      684                     1                684              2                  1,368
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.155(f)                                                            18                     1                 18               .25                   5
--------------------------------------------------------------------------------------------------------------------------------------------------------
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               5,082
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.260(e)                                                         1,694                   365            618,310               .083             51,526
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.265(c)(1)                                                      1,694                 1,196          2,026,024               .083            168,835
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.265(c)(3)                                                        847                     1                847              1                    847
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.265(e)                                                         1,694                 1,196          2,026,024               .083            168,835
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.270(a)                                                         1,694                 1,196          2,026,024               .25             506,506
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.270(e)                                                         1,824                     2              3,648               .30               1,824
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.290(d) and (e)                                                 1,694                    51             86,394               .25              21,599
--------------------------------------------------------------------------------------------------------------------------------------------------------
1271.320(b)                                                         1,141                     5              5,705              1                  5,705
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                                                                          1,967,496
--------------------------------------------------------------------------------------------------------------------------------------------------------
\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).



[[Page 39541]]

    Dated: July 2, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-16804 Filed 7-8-10; 8:45 am]
BILLING CODE 4160-01-S

