[Federal Register Volume 69, Number 17 (Tuesday, January 27, 2004)]
[Rules and Regulations]
[Pages 3823-3826]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-1733]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 1271

[Docket No. 97N-484R]


Human Cells, Tissues, and Cellular and Tissue-Based Products; 
Establishment Registration and Listing

AGENCY: Food and Drug Administration, HHS.

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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 except human dura mater and human heart valve allografts, 
currently subject to application or notification requirements under the 
Federal Food, Drug, and Cosmetic Act (the act), from the scope of the 
definition of ``human cells, tissues, or cellular or tissue-based 
products (HCT/P's)'' subject to the registration and listing 
requirements contained in 21 CFR part 1271. That definition became 
effective on January 21, 2004. FDA is taking this action to assure that 
these products, which are currently subject to the act and therefore 
regulated under the current good manufacturing practice regulations set 
out in the quality system regulations in 21 CFR part 820 are not 
released from the scope of those regulations before a more 
comprehensive regulatory framework applicable to HCT/P's, including 
donor suitability requirements, good tissue practice regulations, and 
appropriate enforcement provisions, is fully in place. When that 
comprehensive framework is in place, FDA intends that human dura mater 
and human heart valves will be subject to it. FDA intends to revoke 
this interim final rule at that time.

DATES: The interim final rule is effective January 23, 2004. The 
compliance date is March 29, 2004. Submit written or electronic 
comments on the interim final rule by April 26, 2004.

ADDRESSES: Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Paula S. McKeever, Center for 
Biologics Evaluation and Research (HFM-17), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
6210.

SUPPLEMENTARY INFORMATION:

I. Background

    In an earlier related rulemaking entitled ``Human Cells, Tissues, 
and Cellular and Tissue-Based Products; Establishment Registration and 
Listing'' (66 FR 5447, January 19, 2001), the agency defined an HCT/P 
as ``articles containing or consisting of human cells or tissues that 
are intended for implantation, transplantation, infusion, or transfer 
into a human recipient.'' Examples of HCT/P's included, but were not 
limited to, ligaments, skin, bone, dura mater, heart valves, corneas, 
peripheral and cord blood hematopoietic stem cells, manipulated 
autologous chondrocytes, oocytes, and spermatozoa (66 FR at 5447 at 
5467).
    That rule further provided that HCT/P's meeting the criteria 
established in part 1271 (21 CFR part 1271) in Sec. 1271.10 would be 
regulated solely under section 361 of the Public Health Service Act 
(the PHS Act) (42 U.S.C. 264). The effect of these two provisions was 
that human dura mater and human heart valve allografts meeting the 
definition of HCT/P and the criteria in Sec. 1271.10 for regulation 
solely under section 361 of the PHS Act would be removed from the scope 
of regulations established under the authority of the act. Instead they 
would be regulated solely under the comprehensive HCT/P regulations 
that the agency intended to issue under the authority of section 361 of 
the PHS Act. The agency intended to replace the current good 
manufacturing practice requirements applicable to human dura mater and 
human heart valve allografts, which provide protection against the 
risks of communicable disease and are set out in the Quality System 
Regulation under part 820 (21 CFR part 820), with donor suitability and 
good tissue practice regulations, which would be developed specifically 
to address the risks of communicable disease transmission.
    Accordingly, at the time the registration and listing rule 
published, FDA had proposed two other rules to establish the remainder 
of that comprehensive regulatory framework:
     Suitability Determination for Donors of Human 
Cellular and Tissue-Based Products (64 FR 52696, September 30, 1999), 
and
     Current Good Tissue Practice for Manufacturers 
of Human Cellular and Tissue-Based Products; Inspection and Enforcement 
(66 FR 1508, January 8, 2001).
    When finalized, these three rules will establish a comprehensive 
regulatory framework for human cellular and tissue-based products, to 
be contained in part 1271. However, because all three regulations were 
not in place at the time the registration and listing rule published, 
the agency delayed, initially for 2 years, the effective date of the 
definition of HCT/P previously quoted. The agency made the registration 
and listing rule effective at first only for products currently 
regulated as human tissue intended for transplantation under 21 CFR 
part 1270. The agency explained that FDA did not intend to begin 
regulating human dura mater and human heart valve allografts that meet 
the criteria for regulation solely under section 361 of the PHS Act 
until the donor-suitability and good tissue practice (GTP) components 
of part 1271 become effective, or other appropriate steps have been 
taken. (66 FR at 5447 at 5453). Because finalizing the remaining two 
rules presented difficult issues and the rulemaking has taken more time 
than initially foreseen, FDA delayed the effective date for an 
additional year, until January 21, 2004 (68 FR 2689, January 21, 2003).
    We (FDA) have now reached that date, and although work on the 
remaining two rules is nearing completion, the rules have not yet 
published. Rather than again delay the effective date of this 
provision, FDA believes that the provision should take effect, provided 
that the agency issues this interim final rule to assure that human 
dura mater and human heart valve allografts remain subject to 
appropriate provisions under the act, and including current good 
manufacturing practice requirements, until the comprehensive regulatory 
framework is in place. (FDA understands that many establishments may 
have reasonably expected FDA to delay the effective date of this 
provision again, because the donor suitability and GTP rules are not 
yet finalized. Once the comprehensive framework is in place, the agency 
intends to revoke this interim final rule, so that the comprehensive 
regulatory framework would then apply to human dura mater and human 
heart valve allografts, and these products would no longer be subject 
to regulation as medical devices under the act.

II. Legal Authority

    FDA is issuing this regulation under the authority of section 361 
of the PHS Act. Under that section, FDA 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. (See sec. 1, Reorg. Plan No. 3 of 1966 at 42 
U.S.C. 202 for delegation of section 361 of the PHS Act authority from 
the Surgeon General to the Secretary of the Department of Health and 
Human Services (the Secretary); See 21 CFR 5.10(a)(4) for delegation 
from the Secretary to FDA.) 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).) Until we put into place the new 
regulatory framework's remaining components, which are intended to

[[Page 3825]]

prevent the introduction, transmission, and spread of communicable 
diseases, it is necessary to preserve the applicability of regulations 
currently applicable to human dura mater and human heart valve 
allografts.

III. Issuance of an Interim Final Rule; Immediate 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 immediately upon filing at the Office of 
the Federal Register.
    FDA concludes that this interim final rule is necessary to assure 
that human dura mater and human heart valve allografts, currently 
subject to good manufacturing practice regulatory requirements under 
the authority of the act, do not lose that protection during an interim 
period occurring between the date of their incorporation into the 
definition of HCT/P (January 21, 2004) and the effective date for the 
tissue donor suitability and GTP rules, to be finalized in the near 
future. Human dura mater and human heart valve allografts present 
significant risks of communicable disease transmission when the 
products are not handled properly. Absent this interim final rule, 
human dura mater and human heart valve allografts would fall within the 
definition of HCT/P's (Sec. 1271.3(d)(2)), and likely would also fall 
within the criteria for regulation solely under section 361 of the PHS 
Act (Sec. 1271.10). This would mean that human dura mater and human 
heart valve allografts would no longer be subject to the quality system 
regulation currently applicable to devices (part 820). If this occurred 
before the donor suitability and GTP rules became final, the public 
would lose the important public health protections afforded by the 
quality system regulation. In light of the significant public health 
risk that would be presented by these products if their manufacture 
were not subject to either a good tissue practice or current good 
manufacturing practice regulation, the Commissioner finds good cause to 
make these regulatory requirements final and effective immediately.
    Although this agency is publishing this regulation as an interim 
final rule without an opportunity for prior notice and comment on a 
proposed rule, FDA is providing opportunity for comment on this interim 
final rule.

IV. Provisions of the Interim Final Rule

    This interim final rule amends Sec. 1271.3(d)(2) to delete the 
words ``dura mater and heart valves'' from the definition of ``Human 
cells, tissues, or cellular or tissue-based products (HCT/P's).'' It 
further adds new Sec. 1271.3(d)(2)(viii), an exception to the 
definition of HCT/P's for human dura mater and human heart valve 
allografts. A minor change was necessary to Sec. 1271.3(d)(2)(vi) and 
(d)(2)(vii) due to the addition of Sec. 1271.3(d)(2)(viii).

V. Analysis of Impacts

    FDA has examined the impacts of the interim final rule under 
Executive Order 12866 and the Regulatory Flexibility Act (Public Law 
104-4), and the Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-
1571), which are not applicable to interim final rules. 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 consistent with the regulatory philosophy 
and principles identified in the Executive order. In addition, the 
interim final rule is not a significant regulatory action as defined by 
the Executive order. Therefore, FDA is not required under the Executive 
order to submit it to Office of Management and Budget (OMB) for review.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of 
proposed and final rules on small entities. Because this rule actually 
narrows the scope of the current regulation, this interim final rule 
does not impose in any new requirements. The agency certifies that the 
interim final rule will not have a significant economic impact on a 
substantial number of small entities. The Regulatory Flexibility Act 
requires no further analysis of this interim final rule.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement of anticipated costs and 
benefits, before issuing any final rule that was the subject of a 
notice of proposed rulemaking and that may result in the expenditure in 
any 1 year by State, local, and tribal governments, in the aggregate, 
or by the private sector, of $100 million or more (adjusted annually 
for inflation). The current inflation adjusted statutory threshold is 
about $110 million. FDA does not expect this interim final rule to 
result in any 1-year expenditure that would meet or exceed this amount. 
FDA is not required to prepare a written statement under the Unfunded 
Mandates Reform Act of 1995.

VI. The Paperwork Reduction Act of 1995

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

VII. Environmental Impact

    The agency has determined under 21 CFR 25.30(i) and 21 CFR 25.30(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, 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.

[[Page 3826]]

List of Subjects

21 CFR Part 1271

    Biologics, Drugs, Human cells and tissue-based products, Medical 
devices, Reporting and recordkeeping requirements.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act, 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
1. The authority citation for 21 CFR part 1271 continues to read as 
follows:

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

0
2. Section 1271.3 is amended by revising the second sentence in the 
introductory text of paragraph (d)(2), by revising paragraphs 
(d)(2)(vi) and (d)(2)(vii), and by adding paragraph (d)(2)(viii) to 
read as follows:


Sec. 1271.3  How does FDA define important terms in this part?

* * * * *
    (d) * * *
    (2) * * * Examples of HCT/P's include, but are not limited to, 
bone, ligament, skin, cornea, hematopoietic stem cells derived from 
peripheral and cord blood, manipulated autologous chondrocytes, 
epithelial cells on a synthetic matrix, and semen or other reproductive 
tissue.* * *
* * * * *
    (vi) Cells, tissues, and organs derived from animals other than 
humans;
    (vii) In vitro diagnostic products as defined in Sec. 809.3(a) of 
this chapter; and
    (viii) Human dura mater and human heart valve allografts.
* * * * *

    Dated: January 21, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-1733 Filed 1-23-04; 8:45 am]
BILLING CODE 4160-01-S