[Printable PDF - 98 KB]    http://www.fda.gov/cber/rules/hctdnr.htm

[Federal Register: June 19, 2007 (Volume 72, Number 117)]
[Rules and Regulations]               
[Page 33667-33669]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr19jn07-11]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1271

[Docket No. 1997N-0484T]

 
Human Cells, Tissues, and Cellular and Tissue-Based Products; 
Donor Screening and Testing, and Related Labeling

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is adopting as a final 
rule, without change, the provisions of the interim final rule that 
amended certain regulations regarding the screening and testing of 
donors of human cells, tissues, and cellular and tissue-based products 
(HCT[sol]Ps), and related labeling. FDA is taking this action to 
complete the rulemaking initiated with the interim final rule.

DATES: This rule is effective June 19, 2007.

FOR FURTHER INFORMATION CONTACT: Brenda R. Friend, Center for Biologics 
Evaluation and Research (HFM-17), Food and Drug Administration, 1401 
Rockville Pike, suite 200N, Rockville, MD 20852-1448, 301-827-6210.

SUPPLEMENTARY INFORMATION:

I. Background

    In the Federal Register of May 25, 2005 (70 FR 29949), FDA issued 
an interim final rule on Human Cells, Tissues, and Cellular and Tissue-
Based Products; Donor Screening and Testing, and Related Labeling 
(hereinafter referred to as the interim final rule). These regulations 
became effective upon the date of publication in the Federal Register. 
We issued the interim rule to assure that the changes became effective 
concurrently with the Eligibility Determination for Donors of Human 
Cells, Tissues, and Cellular and Tissue-Based Products final rule (69 
FR 29786, May 25, 2004) and the Current Good Tissue Practice for Human 
Cell, Tissue, and Cellular and Tissue-Based Product Establishments; 
Inspection and Enforcement final rule (69 FR 68612, November 24, 2004) 
on May 25, 2005. In this way, establishments were not required to take 
steps to comply with the provisions in part 1271 (21 CFR part 1271) 
that were replaced by the changes set out in the interim final rule, 
and certain HCT[sol]Ps would continue to be available.

II. Comments on the Interim Final Rule and FDA Responses

    We received several comments on the interim final rule. To make it 
easier to identify comments and our responses, the word ``Comment,'' in 
parentheses, will appear before the comment's description, and the word 
``Response,'' in parentheses, will appear before our response. We have 
also numbered each comment to help distinguish between different 
comments. The number assigned to each comment is purely for 
organizational purposes and does not signify the comment's value or 
importance or the order in which it was received.
    (Comment 1) A comment appreciated and applauded the change to Sec.  
1271.370(b)(4) to allow labeling with warning(s) to accompany the 
HCT[sol]P when the HCT[sol]P container is too small to accommodate the 
warning(s) on the label. Another comment expressed concern that the 
accompanying labeling could be ignored or lost.
    (Response) We acknowledge and appreciate the supportive comment. 
This requirement addresses the situation where it is not physically 
possible to include warnings directly on the HCT[sol]P label, either 
because the container is too small or the HCT[sol]P is cryopreserved, 
which may interfere with adherence of label materials. In these 
situations, the warnings must accompany the HCT[sol]P.
    We acknowledge the comment's concern that it is better to provide 
information on the HCT[sol]P's label. However, we permit other 
important information, such as the summary of records, to accompany the 
HCT[sol]P; such important information is not present on the HCT[sol]P 
label. We believe that consignees are generally careful to make sure 
information accompanying HCT[sol]Ps is not ignored or lost, and we 
believe that the accompanying information will be available. Necessity 
compels this authorization for certain information to accompany an 
HCT[sol]P when it is not possible to include it on the label, and we 
conclude that it is adequate to provide such information in 
accompanying documents when it is necessary to do so.
    (Comment 2) A comment noted that Sec.  1271.55(a)(1) requirements 
(i.e., affixing a distinct identification code to the HCT[sol]P 
container) were clearly designed to maintain donor anonymity. However, 
the comment asked if fertility clinics could write in information about 
the recipient (e.g., name, account number) because by the time a 
donor's HCT[sol]P is collected, a specific recipient has already been 
identified. The comment stated that fertility clinics, for example, 
never collect anonymously donated oocytes without already having a 
recipient identified and ready to receive the donation.
    (Response) The requirements in Sec.  1271.55(a)(1) are focused on 
protecting the identity of the donor in the interest of 
confidentiality. We note that this provision prescribes how an 
establishment must label the HCT[sol]P before releasing it for 
distribution, but does not prohibit the addition of the recipient's 
name once the donor eligibility determination is completed and the 
reproductive HCT[sol]P is released for distribution. For an oocyte 
donation, the release determination is likely to be completed very soon 
after collection.
    (Comment 3) A few comments suggested changes to the timing of the 
specimen collection in Sec.  1271.80(b). In particular, a comment noted 
that Sec.  1271.80(b)(1) permits testing on oocyte donors up to 30 days 
before recovery, while Sec.  1271.80 seems to maintain a 7-day testing 
window for semen donors, whose spermatozoa will combine with the 
oocytes to create an embryo for a

[[Page 33668]]

gestational carrier cycle, and stated that both these donors should 
have a 30-day testing window.
    Another comment stated that testing donors of sperm, oocytes, and 
embryos at the time of donation is ``superior'' but noted that the 
American Association of Tissue Banks guidelines for accredited tissue 
banks recommend that all donors be tested within 7 days of collection. 
The comment recommended that FDA go back to 7-day testing. One comment 
recommended that any individual intending to cryopreserve his/her 
HCT[sol]P be tested 7 to 10 days prior to cryopreservation or within a 
short period after cryopreservation.
    (Response) The interim final rule modified the timing of blood 
specimen collection for oocyte donors to permit the determination of 
donor eligibility before the donor's conditioning regimen begins. We 
did not change the timing of blood specimen collection for semen 
donors, because they do not undergo any conditioning regimen.
    Collecting blood specimens from donors of semen, oocytes, and 
embryos at the time of donation is sometimes impractical because of the 
time it takes to obtain the test results. We have made exceptions to 
the requirement for testing within 7 days in situations where the donor 
has to undergo conditioning in advance. This is also the case where the 
recipient undergoes myeloablative treatment and there is a need to 
determine the eligibility of the donor before the recipient's 
treatment. Establishments are welcome to establish more restrictive 
testing criteria as noted in the American Association of Tissue Banks 
standards.
    (Comment 4) A comment responded to FDA's solicitation for comments 
on the effectiveness of Sec.  1271.90(a)(4), (a new exception from the 
donor-eligibility determination requirement for certain cryopreserved 
embryos) to enhance the availability of embryos, and the potential 
benefits, risks, and any other direct or indirect effects of this 
change. The comment pointed out that cryopreserved embryos (and 
HCT[sol]Ps) are often exposed to liquid nitrogen, and research articles 
have reported that hepatitis B and bovine hepatitis virus can be 
transmitted through liquid nitrogen contamination. Therefore, 
cryopreserved embryos from untested semen and oocyte donors, 
commingling with cryopreserved embryos from tested donors, may place 
recipients, cryostorage centers, and assisted reproductive technology 
facilities at risk. Simply having warning(s) appear on the label of the 
cryopreserved HCT[sol]P specimen from an untested donor, under revised 
Sec. Sec.  1271.90(b)(2) and (b)(3), or having the warning(s) accompany 
such HCT[sol]Ps, under revised Sec.  1271.370(b)(4), would not 
eliminate the risks and may even result in an increased number of tort 
cases.
    (Response) We decline to require separate storage for tested and 
untested HCT[sol]Ps, though establishments may choose to utilize 
physically separated areas for tested and untested HCT[sol]Ps. To 
reduce risk of contamination/cross-contamination from HCT[sol]Ps that 
are untested or determined ineligible because of a reactive screening 
test, reproductive establishments could verify or validate that the 
cryocontainers (vials or straws) meet specifications and are not 
subject to breakage at the temperatures and conditions at which they 
are stored. Verification could be accomplished by the establishment 
that uses the cryocontainers or by the vendor that supplies the 
cryocontainers.
    (Comment 5) A comment recommended a quarantine period of 6 months 
for any reproductive HCT[sol]P from directed donors and anonymous 
donors, including anonymous donors whose identity might be disclosed. 
The comment also recommended mandatory retesting of oocyte donors (for 
donated embryos created using a donor oocyte) and embryo donors (semen 
and oocyte donors) prior to transfer of the donated HCT[sol]P.
    (Response) In the Eligibility Determination for Donors of Human 
Cells, Tissues, and Cellular and Tissue-Based Products final rule (69 
FR 29786 at 29800), we explained why quarantine and retesting are 
required for anonymous semen donors but not for other reproductive 
donors. We considered comments concerning decreased pregnancy success 
rates for cryopreserved semen from directed donors and for 
cryopreserved embryos. In addition, techniques for the successful 
cryopreservation of oocytes are still being developed. Accordingly, we 
have declined to increase quarantine requirements for oocyte and embryo 
donations.
    (Comment 6) A comment requested clarification on the use of the 
warning ``FOR AUTOLOGOUS USE ONLY'' under Sec.  1271.90(b)(1), and 
particularly, FDA's definition of ``autologous'' for certain 
circumstances related to in vitro fertilization.
    (Response) We define ``autologous'' in Sec.  1271.3(a) as meaning 
the implantation, transplantation, infusion, or transfer of human cells 
or tissue back into the individual from whom the cells or tissue were 
recovered. Transfer of an embryo into the woman who contributed the 
oocytes would not be considered autologous because the embryo is formed 
by gametes from two individuals. This means that in the circumstances 
related to in vitro fertilization, use of a label ``FOR AUTOLOGOUS USE 
ONLY'' would not be appropriate for labeling a cryopreserved embryo. 
Other labeling requirements listed in Sec.  1271.90(b) would apply 
based on the test status of the gamete donors.
    (Comment 7) We received several comments that, although they relate 
to significant issues, are not relevant to the interim final rule. 
These comments concerned: (1) A request that donors with a curable 
communicable disease be eligible to donate reproductive HCT[sol]Ps 
after receiving treatment and retesting negative for the communicable 
disease; (2) the definition of ``responsible person'' under Sec.  
1271.3(t); (3) certification or registration requirements, other than 
those applicable under the Clinical Laboratory Improvement Amendments 
of 1988 (42 U.S.C. 263a), for a clinical laboratory to perform donor 
screening; and (4) issues associated with the storage of embryos and 
other HCT[sol]Ps, but unrelated to the potential for transmission of 
communicable disease (e.g., abandonment, legal responsibility, and 
nonpayment).
    (Response) These comments are on matters outside the scope of the 
interim final rule and this final rule. Relevant communicable disease 
agent or disease was addressed in previously finalized portions of part 
1271, subpart C. The definitions in Sec.  1271.3 were not discussed or 
addressed in the interim final rule. Registration requirements 
applicable to testing laboratories are addressed in part 1271, subparts 
A and B, and certification requirements are discussed in part 1271, 
subpart C. FDA expects that the contractual agreement between the 
cryostorage facility and the individual(s) storing the HCT[sol]P will 
address financial and legal issues unrelated to the potential for 
communicable disease transmission.

III. Analysis of Impacts

    FDA has examined the impacts of the final rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive 
Order 12866 directs agencies to assess all costs and benefits of 
available regulatory alternatives and, when regulation is necessary, to 
select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The analysis of

[[Page 33669]]

costs and benefits of available regulatory alternatives contained in 
the interim final rule (70 FR 29949 at 29951) is adopted without change 
in this final rule. By now reaffirming that interim final rule, FDA has 
not imposed any new requirements. Therefore, there are no additional 
costs and benefits associated with this final rule.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this final rule does not make any changes to 
the interim final rule or our analysis included therein, the agency 
certifies that the final rule will not have a significant economic 
impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before issuing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $122 million, using the most current (2005) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.

IV. The Paperwork Reduction Act of 1995

    This final rule contains no collections of information. Therefore, 
clearance by OMB under the Paperwork Reduction Act of 1995 is not 
required.

V. Environmental Impact

    The agency has determined under 21 CFR 25.30(i) and (j) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.

VI. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the rule 
does not contain policies that have substantial direct effects on the 
States, on the relationship between the National Government and the 
States, or on the distribution of power and responsibilities among the 
various levels of government. Accordingly, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

List of Subjects in 21 CFR Part 1271

    Biological Drugs, Communicable diseases, HIV/AIDS, Human cells, 
tissues, and cellular and tissue-based products, Medical devices, 
Reporting and recordkeeping requirements.

0
Therefore, under the Public Health Service Act, and under authority 
delegated to the Commissioner of Food and Drugs, 21 CFR part 1271 is 
amended as follows:

PART 1271--HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED-
PRODUCTS

0
Accordingly, the interim final rule amending 21 CFR part 1271 which was 
published at 70 FR 29949 on May 25, 2005, is adopted as a final rule 
without change.

    Dated: May 26, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-11795 Filed 6-18-07; 8:45 am]

BILLING CODE 4160-01-S

from FDA Dec 2008

www.embryosalive.com