[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]
=======================================================================
-----------------------------------------------------------------------
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.
[[Page 3824]]
ACTION: Interim final rule; opportunity for public comment.
-----------------------------------------------------------------------
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