[Federal Register Volume 70, Number 100 (Wednesday, May 25, 2005)]
[Rules and Regulations]
[Pages 29949-29952]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-10583]


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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: Interim final rule; opportunity for public comment.

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SUMMARY: The Food and Drug Administration (FDA) is issuing an interim 
final rule to amend certain regulations regarding the screening and 
testing of donors of human cells, tissues, and cellular and tissue-
based products (HCT/Ps), and related labeling. FDA is taking this 
action in response to comments from affected interested persons 
regarding the impracticability of complying with certain regulations as 
they affect particular HCT/Ps.

DATES: The interim final rule is effective May 25, 2005. Submit written 
or electronic comments on the interim final rule by August 23, 2005.

ADDRESSES: You may submit comments, identified by Docket No. 1997N-
0484T, by any of the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: http://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
     E-mail: [email protected]. Include Docket No. 1997N-
0484T in the subject line of your e-mail message.
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the agency name 
and Docket No. for this rulemaking. All comments received will be 
posted without change to http://www.fda.gov/ohrms/dockets/default.htm, 
including any personal information provided. For detailed instructions 
on submitting comments and additional information on the rulemaking 
process, see section IX in the SUPPLEMENTARY INFORMATIONsection of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number, found in brackets in the heading of this 
document, into the ``Search'' box and follow the prompts and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Paula S. McKeever, 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

    We (FDA), have issued three final rules to implement a 
comprehensive new system for regulating HCT/Ps in part 1271 (21 CFR 
part 1271). The final rules are as follows:
     Human Cells, Tissues, and Cellular and Tissue-Based 
Products; Establishment Registration and Listing (66 FR 5447, January 
19, 2001) (registration final rule);
     Eligibility Determination for Donors of Human Cells, 
Tissues, and Cellular and Tissue-Based Products (69 FR 29786, May 25, 
2004) (donor-eligibility final rule); and
     Current Good Tissue Practice for Human Cell, Tissue, and 
Cellular and Tissue-Based Product Establishments; Inspection and 
Enforcement (69 FR 68612, November 24, 2004) (CGTP final rule).
    This interim final rule is making changes in response to comments 
from affected interested persons regarding the impracticability of 
complying with certain regulations as they affect particular HCT/Ps, as 
well as certain other editorial changes.

II. Legal Authority

    We are issuing these regulations under the authority of section 361 
of the

[[Page 29950]]

Public Health Service Act (PHS Act) (42 U.S.C. 264). By authority 
delegated under that section, we may make and enforce regulations 
necessary to prevent the introduction, transmission, or spread of 
communicable diseases between the States or from foreign countries into 
the States. Intrastate transactions affecting interstate communicable 
disease transmission may also be regulated under section 361 of the PHS 
Act. (See Louisiana v. Mathews, 427 F. Supp. 174, 176 (E.D. La. 1977).) 
This interim final rule addresses the impracticability of complying 
with certain regulations that affect particular HCT/Ps.

III. Issuance of an Interim Final Rule; Effective Date

    Under the provisions of the Administrative Procedure Act at 5 
U.S.C. 553(b)(B) and FDA's administrative practices and procedures 
regulations at Sec.  10.40(e)(1) (21 CFR 10.40(e)(1)), the Commissioner 
of Food and Drugs (the Commissioner) finds that use of prior notice and 
comment procedures for issuing this interim final rule is contrary to 
the public interest. In addition, the Commissioner finds good cause 
under 5 U.S.C. 553(d)(3) and Sec.  10.40(c)(4)(ii) for making this 
interim final rule effective May 25, 2005.
    We conclude that this interim final rule is necessary to assure 
that the changes become effective concurrently with the donor-
eligibility final rule and the CGTP final rule on May 25, 2005. In this 
way, establishments will not be required to take steps to comply with 
the provisions that will be replaced by the changes set out in this 
rule, and certain HCT/Ps will continue to be available. If the rule is 
not effective immediately (before the agency could take comment on a 
proposed rule and issue a final rule), delay could result in certain 
HCT/Ps being unavailable for donation. Based on existing donation 
practices, we believe that delay would increase the risk that some 
patients will not be able to obtain certain donated HCT/Ps.
    Although we are publishing this regulation as an interim final rule 
without prior notice and comment on a proposed rule, we are providing 
opportunity for comment on this interim final rule. After reviewing 
public comment submitted to the docket, we will issue a final rule.

IV. Provisions of the Interim Final Rule

    We are making the following changes to part 1271.

A. Sections 1271.55 and 1271.290

    Section 1271.55 describes:
     The records that must accompany the HCT/P at all times 
once the donor-eligibility determination is made (Sec.  1271.55(a));
     The summary of records used to make the donor-eligibility 
determination (Sec.  1271.55(b));
     The deletion of personal information (Sec.  1271.55(c)); 
and
     The record retention requirements (Sec.  1271.55(d)).
    Section 1271.55(a)(1) requires you to affix a distinct 
identification code to the HCT/P container, e.g., an alphanumeric, that 
relates the HCT/P to the donor and to all records pertaining to the 
HCT/P. In the interest of confidentiality, the distinct identification 
code must not include an individual's name, social security number, or 
medical record number. We make an exception to this prohibition for 
autologous or directed reproductive donations because in such 
donations, the donor is already known to the recipient.
    This interim final rule adds to this exception donations made by 
first-degree or second-degree blood relatives. Donors who are first-
degree or second-degree blood relatives know and are known by the 
recipient, similar to directed reproductive donations. Adding this 
exception may increase the comfort of the recipient by helping to 
confirm that the HCT/P is from the designated donor.
    The revision to Sec.  1271.290 is a technical change to reference 
the provisions in Sec.  1271.55(a)(1).

B. Section 1271.80

    Section 1271.80 describes the general requirements for donor 
testing, such as:
     The requirement to test for relevant communicable 
diseases;
     Timing of specimen collection;
     What tests to use; and
     Who is an ineligible donor.
    The interim final rule revises the requirements regarding timing of 
the specimen collection. We deleted the statement in Sec.  1271.80(b) 
regarding specimen collection at the time of recovery, because we are 
aware that this has been interpreted to mean that a testing specimen 
collected from a donor on the day of donation is superior. We believe 
that, for a cadaveric donor, either a pre-mortem specimen collected 
within 7 days before death or a post mortem specimen are appropriate 
specimens. However, the pre-mortem specimen, if available, may be 
preferable because it is likely to be less hemolyzed, and excessive 
hemolysis can interfere with the test results. In addition, a cadaveric 
donor may have received fluid infusions prior to death, resulting in 
plasma dilution sufficient to affect test results. For these reasons, a 
specimen collected on the day of donation from a cadaveric donor may 
not be superior to a specimen collected within 7 days before death.
    The interim final rule also modifies the timing of sample 
collection for donors of bone marrow (when considered an HCT/P under 
Sec.  1271.3(d) (21 CFR 1271.3(d))) and oocytes. The change will permit 
the collection of a donor specimen for testing up to 30 days before 
recovery of the HCT/P for these additional HCT/Ps. In the donor-
eligibility final rule we state that we permit collection of the donor 
specimen up to 30 days before recovery for donors of peripheral blood 
stem/progenitor cells due to the myeloablative treatment regimen and 
the need to determine the eligibility of the donor before the 
recipient's treatment begins (69 FR 29786 at 29808). Because this 
reasoning also applies to donors of bone marrow covered by the HCT/P 
regulations and donors of oocytes who must undergo conditioning 
regimens beginning more than 7 days before recovery of oocytes, we have 
included a reference to bone marrow and oocytes in Sec.  1271.80(b) to 
permit testing up to 30 days before recovery.

C. Section 1271.90

    Section 1271.90(a) describes exceptions to the requirement for 
donor-eligibility determination and related labeling requirements. The 
exceptions apply to the following HCT/Ps:
     Cells and tissues for autologous use;
     Reproductive cells or tissue donated by a sexually 
intimate partner of the recipient; and
     Cryopreserved cells or tissue for reproductive use, other 
than embryos, intended for directed donation.
    In the donor eligibility final rule at Sec.  1271.90(a)(2), a donor 
eligibility determination is not required for reproductive cells or 
tissue donated by a sexually intimate partner of the recipient for 
reproductive use. We are now adding a new exemption from screening and 
testing in Sec.  1271.90(a)(4) for cryopreserved embryos that, while 
originally exempt from the donor eligibility requirement because the 
donors were sexually intimate partners, are later intended for directed 
or anonymous donation. When possible, appropriate measures should be 
taken to screen and test the semen and oocyte donors before transfer of 
the embryo to a recipient.
    This change reflects the fact that sexually intimate partners may 
decide to donate their cryopreserved embryos long after their fertility 
treatments are completed. Because the embryos were

[[Page 29951]]

intended for use in a sexually intimate relationship, the donors would 
not have been required to be screened and tested for communicable 
disease agents at the time that oocytes and semen were recovered. The 
new provision recommends that appropriate measures be taken to screen 
and test the semen and oocyte donors before transfer of the embryo to 
the recipient, when possible.
    If appropriate screening and testing of the semen and oocyte donors 
are performed subsequent to cryopreservation and before transfer of the 
embryo to the recipient, the labeling requirement in Sec.  
1271.90(b)(6) applies, i.e., ``Advise recipient that screening and 
testing of the donor(s) were not performed at the time of 
cryopreservation of the reproductive cells or tissue, but have been 
performed subsequently.'' If screening and testing of the semen and 
oocyte donors are not performed, this rule would not prohibit the 
transfer of the embryo into a recipient. In such an event, the labeling 
requirements in Sec.  1271.90(b)(2) and (b)(3) are applicable. The HCT/
P must be labeled with ``NOT EVALUATED FOR INFECTIOUS SUBSTANCES'' and 
``WARNING: Advise recipient of communicable disease risks.'' This 
labeling would provide information to the treating physician to permit 
discussion with the recipient of the potential risks.
    Since we issued the donor eligibility rule, we have received 
letters and comments in meetings concerning the importance of 
cryopreserved embryos to individuals seeking access to donated embryos. 
Donated embryos may provide a very important treatment to some 
individuals. For example, a couple may not be able to conceive a child 
because the female partner has had her ovaries removed and the male 
partner has undergone chemotherapy and no longer has viable 
spermatozoa. In order to assure that such a treatment continues to be 
available, we have re-evaluated the screening and testing requirements 
imposed by these rules. Screening and testing of semen and oocyte 
donors is recommended given the potential risk that such tissue, like 
any cell or tissue derived from the human body, could transmit 
communicable disease. However, it is possible that the couple would not 
be available for screening and testing due to refusal of a partner or 
death. In such instances, the embryo would be labeled as required under 
the rule, and this rule would not prohibit the transfer of the embryo.
    We believe this change will enhance the availability of embryos for 
donation. However, we are soliciting comments on the effectiveness of 
this change to enhance the availability of embryos, and the potential 
benefits, risks, and any other direct or indirect effects of this 
change. Section 1271.90(b) contains labeling requirements for the 
previously described HCT/Ps excepted from the donor-eligibility 
determination requirements. We are revising Sec.  1271.90(b) to clarify 
when each required label is appropriate for the HCT/Ps described in 
Sec.  1271.90(a), i.e., autologous cells and tissues, reproductive 
cells and tissues donated by a sexually intimate partner, and 
cryopreserved reproductive cells and tissues, including embryos, where 
the donor(s) was not screened and tested at the time of collection. We 
have also clarified Sec.  1271.90(b)(3), that cells and tissues for 
autologous use do not require the label ``Advise patient of 
communicable disease risk'' because the patient's own cells or tissues 
are being returned, and in this situation, there is minimal, if any, 
risk.

D. Section 1271.370

    Section 1271.370 contains labeling requirements in addition to 
Sec. Sec.  1271.55, 1271.60, 1271.65, and 1271.90 for HCT/Ps regulated 
solely under section 361 of the PHS Act and part 1271, e.g., distinct 
identification code, expiration date, and warnings. We are revising 
Sec.  1271.370(b)(4) to state that if applying the applicable warnings 
to the container is physically impossible, then the labeling must, 
instead, accompany the HCT/P. This change is necessary because the 
container for some HCT/Ps, such as those used for semen 
cryopreservation, is so small that it does not accommodate the warning 
language. In addition, the use of a tie-tag with warning language is 
not feasible because it is difficult to securely attach the tie-tag to 
a container stored in liquid nitrogen. In such cases, the warning 
language must accompany the HCT/P.

V. Analysis of Impacts

    FDA has examined the impacts of the interim final rule under 
Executive Order 12866 as well as under 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 agency believes that this interim final rule is not an 
economically significant regulatory action under the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this rule makes certain issued regulations 
affecting reproductive and hematopoietic stem cell HCT/Ps more 
practicable, and does not impose any new requirements, FDA certifies 
that the interim 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 $115 million, using the most current (2003) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
interim final rule to result in any 1-year expenditure that would meet 
or exceed this amount.

VI. The Paperwork Reduction Act of 1995

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

VII. 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.

VIII. Federalism

    FDA has analyzed this interim final rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the interim final 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 interim final rule does not contain 
policies that have federalism implications as defined in the Executive 
order and,

[[Page 29952]]

consequently, a federalism summary impact statement is not required.

IX. Request for Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this interim 
final rule. Submit a single copy of electronic comments or two paper 
copies of any mailed comments, except that individuals may submit one 
paper copy. Comments are to be identified with the docket number found 
in brackets in the heading of this document. Received comments may be 
seen in the Division of Dockets Management between 9 a.m. and 4 p.m., 
Monday through Friday.

List of Subjects in 21 CFR 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, Chapter I of title 21 
of the Code of Federal Regulations is amended as follows:

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

0
1. The authority citation for 21 CFR part 1271 continues to read as 
follows:

    Authority: 42 U.S.C. 216, 243, 263a, 264, 271.

0
2. Section 1271.55 is amended by revising paragraph (a)(1) to read as 
follows:


Sec.  1271.55  What records must accompany an HCT/P after the donor-
eligibility determination is complete; and what records must I retain?

    (a) * * *
    (1) A distinct identification code affixed to the HCT/P container, 
e.g., alphanumeric, that relates the HCT/P to the donor and to all 
records pertaining to the HCT/P and, except in the case of autologous 
donations, directed reproductive donations, or donations made by first-
degree or second-degree blood relatives, does not include an 
individual's name, social security number, or medical record number;
* * * * *

0
3. Section 1271.80 is amended by revising paragraph (b) to read as 
follows:


Sec.  1271.80  What are the general requirements for donor testing?

* * * * *
    (b) Timing of specimen collection. You must collect the donor 
specimen for testing at the time of recovery of cells or tissue from 
the donor; or up to 7 days before or after recovery, except:
    (1) For donors of peripheral blood stem/progenitor cells, bone 
marrow (if not excepted under Sec.  1271.3(d)(4)), or oocytes, you may 
collect the donor specimen for testing up to 30 days before recovery; 
or
    (2) In the case of a repeat semen donor from whom a specimen has 
already been collected and tested, and for whom retesting is required 
under Sec.  1271.85(d), you are not required to collect a donor 
specimen at the time of each donation.
* * * * *

0
4. Section 1271.90 is amended by revising paragraphs (a)(3) 
introductory text and (b), and by adding paragraph (a)(4) to read as 
follows:


Sec.  1271.90  Are there exceptions from the requirement of determining 
donor eligibility, and what labeling requirements apply?

    (a) * * *
    (3) Cryopreserved cells or tissue for reproductive use, other than 
embryos, originally exempt under paragraphs (a)(1) or (a)(2) of this 
section at the time of donation, that are subsequently intended for 
directed donation, provided that
* * * * *
    (4) A cryopreserved embryo, originally exempt under paragraph 
(a)(2) of this section at the time of cryopreservation, that is 
subsequently intended for directed or anonymous donation. When 
possible, appropriate measures should be taken to screen and test the 
semen and oocyte donors before transfer of the embryo to the recipient.
    (b) Required labeling. As applicable, you must prominently label an 
HCT/P described in paragraph (a) of this section as follows:
    (1) ``FOR AUTOLOGOUS USE ONLY,'' if it is stored for autologous 
use.
    (2) ``NOT EVALUATED FOR INFECTIOUS SUBSTANCES,'' unless you have 
performed all otherwise applicable screening and testing under 
Sec. Sec.  1271.75, 1271.80, and 1271.85. This paragraph does not apply 
to reproductive cells or tissue labeled in accordance with paragraph 
(b)(6) of this section.
    (3) Unless the HCT/P is for autologous use only, ``WARNING: Advise 
recipient of communicable disease risks,''
    (i) When the donor-eligibility determination under Sec.  1271.50(a) 
is not performed or is not completed; or
    (ii) If the results of any screening or testing performed indicate:
    (A) The presence of relevant communicable disease agents and/or
    (B) Risk factors for or clinical evidence of relevant communicable 
disease agents or diseases.
    (4) With the Biohazard legend shown in Sec.  1271.3(h), if the 
results of any screening or testing performed indicate:
    (i) The presence of relevant communicable disease agents and/or
    (ii) Risk factors for or clinical evidence of relevant communicable 
disease agents or diseases.
    (5) ``WARNING: Reactive test results for (name of disease agent or 
disease),'' in the case of reactive test results.
    (6) ``Advise recipient that screening and testing of the donor(s) 
were not performed at the time of cryopreservation of the reproductive 
cells or tissue, but have been performed subsequently,'' for paragraphs 
(a)(3) or (a)(4) of this section.

0
5. Section 1271.290 is amended by revising the second sentence in 
paragraph (c) to read as follows:


Sec.  1271.290  Tracking.

* * * * *
    (c) * * * Except as described in Sec.  1271.55(a)(1), you must 
create such a code specifically for tracking, and it may not include an 
individual's name, social security number, or medical record number. * 
* *
* * * * *

0
6. Section 1271.370 is amended by revising paragraph (b)(4) to read as 
follows:


Sec.  1271.370  Labeling.

* * * * *
    (b) * * *
    (4) Warnings required under Sec.  1271.60(d)(2), Sec.  
1271.65(b)(2), or Sec.  1271.90(b), if applicable and physically 
possible. If it is not physically possible to include these warnings on 
the label, the warnings must, instead, accompany the HCT/P.
* * * * *

    Dated: May 23, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-10583 Filed 5-24-05; 8:45 am]
BILLING CODE 4160-01-S