[Federal Register: December 28, 2007 (Volume 72, Number 248)]
[Rules and Regulations]
[Page 73589-73602]
[DOCID:fr28de07-9]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 312, 314, 601, 610, 801, 807, 809, 812, and 814

[Docket No. 2006N-0466]

Exceptions or Alternatives to Labeling Requirements for Products
Held by the Strategic National Stockpile

AGENCY: Food and Drug Administration, HHS.

ACTION: Interim final rule; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is issuing regulations
to permit FDA Center Directors to grant exceptions or alternatives to
certain regulatory labeling requirements applicable to human drugs,
biological products, or

medical devices that are or will be included in the Strategic National
Stockpile (SNS). Under this rule, the appropriate FDA Center Director
may grant an exception or alternative to such labeling requirements if
he or she determines that compliance with the requirements could
adversely affect the safety, effectiveness, or availability of
specified lots, batches, or other units of human drugs, biological
products, or medical devices that are or will be included in the SNS,
including not only those that are approved, licensed, or cleared for
marketing, but also those that are investigational. A grant of an
exception or alternative under these regulations will include any
safeguards or conditions deemed appropriate by the FDA Center Director
to ensure that the labeling of such products includes information for
the safe and effective use of the products given their anticipated
circumstances of use. This rule will facilitate the safety,
effectiveness, and availability of appropriate medical countermeasures
in the event of a public health emergency.

DATES: The interim final rule is effective on December 28, 2007. Submit
written or electronic comments on the interim final rule by March 27,
2008. Submit written or electronic comments regarding the information
collection by January 28, 2008 to the Office of Management and Budget
(OMB) (see ADDRESSES).

ADDRESSES: You may submit comments, identified by Docket No. 2006N-
0466, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     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.
Written Submissions
    Submit written submissions in the following ways:
     FAX:<PHONE_NUMBER>.
     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.
    To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name
and docket number for this rulemaking. All comments received may be
posted without change to http://www.fda.gov/ohrms/dockets/default.htm,

including any personal information provided. For additional information
on submitting comments, see the ``Request for Comments'' heading of the
SUPPLEMENTARY INFORMATION section 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.
    Information Collection Provisions: Submit written comments on the
information collection provisions to the Office of Information and
Regulatory Affairs, Office of Management and Budget (OMB). 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:<PHONE_NUMBER>.

FOR FURTHER INFORMATION CONTACT: For information concerning human
biological products: Stephen Ripley, Center for Biologics Evaluation
and Research (HFM-17), Food and Drug Administration, 1401 Rockville
Pike, suite 200N, Rockville, MD 20852-1448,<PHONE_NUMBER>.
    For information concerning human drug products: Brad G. Leissa,
Center for Drug Evaluation and Research, Food and Drug Administration,
Mail Stop 1603, 10903 New Hampshire Ave., White Oak Complex, Building
21, Room 1624, Silver Spring, MD 20993,<PHONE_NUMBER>.
    For information concerning medical devices: Casper E. Uldriks,
Center for Devices and Radiological Health, Food and Drug
Administration, 2094 Gaither Rd., rm. 229, Rockville, MD 20850, 301-
276-0106.

SUPPLEMENTARY INFORMATION:

I. Introduction

    This interim final rule applies to human drugs, biological
products, and medical devices (hereinafter referred to collectively as
medical products) that are or will be held in the SNS, including those
SNS assets that are held at the manufacturer's facility or elsewhere on
behalf of the SNS (e.g., vendor managed inventory that is distributed,
held, and managed by manufacturers or commercial distributors for the
SNS) and prepositioned locations (e.g., CHEMPACKs that are distributed,
held, and managed by hospitals and other facilities for the SNS).
    An act of terrorism or a natural disaster event may result in the
need for rapid access to large quantities of medical products. Under
the Public Health Service Act (PHS Act), the Department of Health and
Human Services (HHS) stockpiles medical products that are essential to
the health security of the Nation. (See PHS Act section 319F-2, 42
U.S.C. 247d-6b)). This collection of medical products , known as the
SNS, is to ``provide for the emergency health security of the United
States, including the emergency health security of children and other
vulnerable populations, in the event of a bioterrorist attack or other
public health emergency.'' The SNS is maintained by the Assistant
Secretary for Preparedness and Response (ASPR), exercising this
responsibility and authority of the Secretary, in collaboration with
the Director of the Centers for Disease Control and Prevention (CDC),
and in coordination with the Department of Homeland Security. Examples
of situations that may necessitate the deployment of such products from
the SNS are:
     Acts of terrorism using chemical, biological,
radiological, or nuclear agents;
     Mass trauma; or
     Natural disasters such as hurricanes, pandemics, or
earthquakes.
    The SNS is also designed to augment similar stockpiles of medical
supplies held by State and local public health agencies for use in the
event of a national emergency.

II. Background

    It may be appropriate for certain medical products that are or will
be held in the SNS to be labeled in a manner that would not comply with
certain FDA labeling regulations, given their anticipated circumstances
of use in an emergency. However, noncompliance with these labeling
requirements could render such products misbranded under section 502 of
the Federal Food, Drug, and Cosmetic Act (the FFD&C Act or the act) (21
U.S.C. 352).
    Under this rule, the appropriate FDA Center Director may grant an
exception or alternative to certain FDA labeling requirements if
compliance with the requirements could adversely affect the safety,
effectiveness, or availability of products that are or will be in the
SNS. An exception or alternative granted

under this rule may include conditions or safeguards so that the
labeling for such products includes appropriate information necessary
for the safe and effective use of the product given the product's
anticipated circumstances of use.
    Issues relating to the labeling of products that are or will be in
the SNS exist now and will likely continue to develop. Such labeling
issues may arise as a result of many different factors, including the
indicated use, the storage location, the necessary storage conditions
for a particular product, or the unique distribution mechanisms that
may be used in an emergency. The provisions of this rule apply only to
medical products that are or will be included in the SNS.
    The medical products that may be stockpiled in the SNS include not
only those that are approved, licensed, or cleared for marketing, but
also those that are investigational.\1\ When HHS procures
investigational medical products for the SNS (i.e., products for which
investigational new drug (IND) applications or investigational device
exemptions (IDE) are in effect), it anticipates that these products may
eventually become licensed, approved, or cleared for marketing by FDA
while the products remain stockpiled. Labels on investigational
products, however, including those in the SNS, ordinarily would not
contain all elements required on licensed, approved, or cleared product
labels.
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    \1\Medical products stockpiled in the SNS may also include
products that will ultimately be used in an emergency under section
564 of the FFD&C act (21 U.S.C. 360bbb-3) (regarding Emergency Use
Authorizations).
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    For example, certain information may not be available until after
approval of the product. For licensed biological products, Sec.  610.60
(21 CFR 610.60) requires the container label to include, among other
things, the expiration date of the product and license number of the
manufacturer. Similarly, Sec.  201.17 (21 CFR 201.17), which applies to
drugs, sets forth requirements regarding placement of an expiration
date, when required, on the immediate container. This information may
not be available for an investigational product and thus could not be
placed on container labels if the investigational product was added to
the SNS. (See section III.D of this document for a discussion of
conditions or safeguards that may be imposed in connection with an
alternative or exception granted under this rule to ensure that
labeling includes information necessary for safe and effective use of
the product.)
    Similarly, for medical devices that are restricted to use by
prescription, Sec.  801.109 (21 CFR 801.109) requires that the device
label, other than for surgical instruments, bear a statement
restricting sale of the device by order of a healthcare practitioner
licensed by the law of the State in which he practices (Sec.
801.109(b)(1)). Whether a particular investigational device will be
limited to sale by prescription may not be known before approval or
clearance and, thus, this statement could not be placed on the
investigational device's label if the product was still investigational
when the device was added to the SNS. Additionally, the label of
approved or cleared in vitro diagnostic products (IVDs) must contain
information, such as warnings for users and storage instructions, that
may not be finalized until product approval or clearance and could not
be placed on the label if the investigational products were added to
the SNS (see Sec.  809.10).
    Prior to the implementation of this rule, when such investigational
products were ultimately approved for marketing, the products would
have been subject to relabeling, a potentially time-consuming, costly,
and labor-intensive process given that the SNS can contain large
numbers of these products. The SNS does not have manufacturing
facilities or equipment necessary to relabel products that the SNS
stores. Therefore, it is not feasible for SNS personnel to relabel
products that are physically located in SNS storage sites. Prior to the
implementation of this rule, the products would have needed to be
returned to the manufacturers or sent to relabelers in order to be
relabeled. Requiring relabeling of such investigational medical
products after approval, licensure, or clearance could adversely affect
the safety, effectiveness, or availability of these medical products in
a number of ways. For example, shipping certain products from the SNS
storage sites to the manufacturer or a relabeler for relabeling could
subject them to unacceptable temperature deviations and create
opportunities for product mishandling, such as mixing of different
batches of the same product. Relabeling is especially difficult for
certain products that must be stored at extremely low temperatures. In
some instances, relabeling could cause the product to be unavailable
for dispensing, delay deployment of the product for use, or could
result in reduced product quality (e.g., potency or stability) and the
loss of critical products. Security issues may also affect
availability, as there is the potential for sabotage and diversion if a
product were shipped back to the manufacturer or to a relabeler.
    For these reasons, as explained in the following section of this
document, this rule allows FDA Center Directors to grant exceptions or
alternatives to certain labeling requirements not explicitly required
by statute for medical products that are or will be included in the
SNS.

III. Provisions of the Interim Final Rule

A. Applicability of a Request for an Exception or Alternative

    Under Sec. Sec.  201.26, 610.68, 801.128, and 809.11 (21 CFR
201.26, 610.68, 801.128, and 809.11), the appropriate FDA Center
Director may grant a request for an exception or alternative to certain
regulatory provisions pertaining to the labeling of human drugs,
biological products, and medical devices that currently are or will be
included in the SNS if certain criteria are met. Any grant of an
exception or alternative will only apply to the specified lots,
batches, or other units of medical products in the request. We request
comments on whether the scope of the rule should be amended to extend
to medical products in other Federal, State, and local stockpiles, and
if so, to which stockpile(s) the rule should apply.
    The appropriate FDA Center Director will only review requests for
exceptions or alternatives to the labeling provisions specified in this
rule. The rule is not intended to provide a mechanism for waiving
applicable requirements of sections 502 and 503 (21 U.S.C. 353) of the
FFD&C Act and/or section 351 of the PHS Act. For example, under this
new rule, an SNS official (or a manufacturer with an SNS official's
written concurrence) may submit to FDA a request for an exception or
alternative to a regulatory provision identified in this rule, such as
where an expiration date may be placed under Sec.  201.17, but not to
the requirements under the PHS Act that the package (not necessarily
the container) of a biological product be plainly marked with the
product's expiration date (section 351(a)(1)(B)(iii) of the PHS Act (42
U.S.C. 262(a)(1)(B)(iii))). To the extent that a request for an
exception or alternative to labeling requirements under this rule
implicates other regulations not specified in this rule (e.g.,
regulations in 21 CFR part 211, Current Good Manufacturing Practice for
Finished Pharmaceuticals) or involves statutory requirements, FDA will
limit its consideration of the exception or alternative request to the
labeling provisions specified in this rule. The remaining portions of
such a request or

other requests (i.e., those that do not involve the labeling provisions
specified in this rule) will be reviewed under other applicable waiver
provisions, if any.
    We note that FDA's authority to grant an exception or alternative
to the regulatory provisions specified in the rule is distinct from the
agency's authority to exercise enforcement discretion (i.e., decide not
to take or recommend enforcement action) with respect to statutory and
regulatory requirements, including those involving product labeling
(see Heckler v. Chaney, 470 U.S. 821 (1985)).
    In granting an exception or alternative under this rule, the
appropriate FDA Center Director will consider whether compliance with
the labeling requirements specified in this rule could adversely affect
the safety, effectiveness, or availability of medical products that are
or will be included in the SNS. As previously explained in this
document, relabeling these medical products in compliance with certain
FDA labeling regulations could adversely affect the safety,
effectiveness, or availability of the products in some circumstances.
In those instances, the appropriate FDA Center Director may grant an
exception or alternative to the labeling requirements specified in this
rule. On the other hand, there may be some products for which full or
partial relabeling in compliance with the labeling requirements
specified by this rule will not adversely affect the safety,
effectiveness, or availability of the products. In such cases, an
exception or alternative to the labeling requirements specified in this
rule would not be warranted.
    On a case-by-case basis, the appropriate FDA Center Director may
also determine when an exception or alternative is granted that certain
safeguards and conditions are appropriate, such as additional labeling
on the SNS products, so that the labeling of such products would
include information needed for safe and effective use under the
anticipated circumstances of use.

B. Who May Submit a Request

    A request for an exception or alternative to the labeling
requirements specified in this rule may be submitted by an SNS
official, or by any entity that manufactures (including labeling,
packing, repackaging, or relabeling), distributes, or stores the
medical products subject to the request. Requests from entities other
than the SNS must be submitted with an SNS official's written
concurrence. We believe that many of the requests under this rule will
be submitted by manufacturers, with concurrence of SNS officials, prior
to or at the time a specified lot, batch, or other unit of product is
procured by the SNS, or when an investigational product held in the SNS
has been approved, licensed, or cleared. We anticipate that SNS
officials will also submit requests.
    The appropriate FDA Center Director may also grant an exception or
alternative to the labeling provisions specified in this rule at his or
her own initiative.

C. Request Criteria

    Except when initiated by an FDA Center Director, a request for an
exception or alternative to the labeling requirements specified in this
rule will be in writing and must contain:
     An identification of the specific lot, batch, or other
unit of product, which are or will be in the SNS, that would be subject
to the exception or alternative;
     An identification of the specific labeling provisions
under this rule that are the subject of the request;
     An explanation of why compliance with the specified
labeling provisions could adversely affect the safety, effectiveness,
or availability of the product subject to the request;
     A description of any proposed safeguards or conditions to
be implemented so that the labeling of the product includes appropriate
information necessary for the safe and effective use of the product
given the anticipated circumstances of use;
     Copies of the proposed labeling of the specified lots,
batches, or other units of product that will be subject to the
exception or alternative; and
     Any other information requested by the appropriate FDA
Center Director.

D. Granting of the Request

    When the appropriate FDA Center Director grants or denies a request
for an exception or alternative to the labeling requirements specified
in this rule, the FDA Center Director will convey this decision in
writing. In the written decision, the FDA Center Director may also
impose appropriate conditions or safeguards so that the labeling of the
product includes appropriate information necessary for the safe and
effective use of the product given the anticipated circumstances of
use. Such safeguards or conditions need not be limited to those
proposed in the request, nor do they need to include all conditions or
safeguards proposed in the request. Conditions could include, for
example, a requirement of additional labeling on the SNS product, such
as including the statement ``For Strategic National Stockpile Use
Only'' on the label or elsewhere within the product's labeling. Such
conditions could also address how or where any packaging or labeling
changes would be conducted, or with what personnel. For example, the
manufacturer may be required to take additional steps to ensure that
products licensed, approved, or cleared while in the SNS bear
information in their outer package labeling that was not available when
such products entered the SNS as investigational products.
    After the request is granted, the manufacturer may need to report
to FDA any resulting changes to the New Drug Application (NDA),
Biologics License Application (BLA), Premarket Approval Application
(PMA), or Premarket Notification (510(k)) in effect, if any. The
submission and grant of a request for an exception or alternative to
the labeling requirements specified in this rule may be used to satisfy
certain reporting obligations relating to changes to product
applications under Sec.  314.70 (21 CFR 314.70) (human drugs), Sec.
601.12 (21 CFR 601.12) (biological drugs), Sec.  814.39 (21 CFR 814.39)
(medical devices subject to premarket approval), or Sec.  807.81 (21
CFR 807.81) (medical devices subject to premarket notification
submission (510(k) clearance) requirements). Specifically, because the
information affecting the premarket application will already be
reviewed and approved as part of the request for an exception or
alternative, manufacturers of medical products to which annual or
periodic reporting requirements apply must describe such changes in
their annual (or periodic) reports but are not required to submit
supplement(s) to an approved application describing this information.
This will reduce regulatory burden on industry by reducing duplication
of regulatory submissions. Supplements under 21 CFR 814.39 and periodic
reports under Sec.  814.84 are not required for medical devices with
510(k) clearance, however. For these devices, the Center Director may
determine that the submission and grant of a written request for an
exception or alternative under this rule satisfies the 510(k)
submission requirements in Sec.  807.81(a)(3).

E. Labeling Provisions Subject to Exception or Alternative

    We are listing in Sec. Sec.  201.26(f) (human drug products),
610.68(f) (biological products), 801.128(f) (medical devices), and
809.11(f) (in vitro diagnostic products) those labeling provisions for
which the appropriate FDA Center Director may grant an exception or
alternative. As indicated in section III.A

of this document, requests for exceptions or alternatives to other
requirements of FDA's labeling regulations (such as bar code label
requirements), or to other general regulations or statutory provisions,
will be handled under any waiver provisions that may be applicable to
those statutory or regulatory requirements. Additionally, FDA may
exercise enforcement discretion with respect to the labeling
requirements specified in this rule or other regulatory and statutory
requirements.
1. Human Drug Products (Sec.  201.26(f))
    For human drug products, including biological drugs, the following
requirements pertaining to labeling in part 201, subpart A (21 CFR part
201, subpart A) and Sec.  312.6 (21 CFR 312.6) may be the subject of an
exception or alternative under this rule, except to the extent that
they are explicitly required by statute:
     Identification of persons other than the manufacturer,
packer, or distributor (Sec.  201.1(h)(1));
     Appearance of a person's name without qualification on the
label (Sec.  201.1(h)(2));
     Appropriate qualifying phrases for the identity of the
distributor or packer (Sec.  201.1(h)(5) and (h)(6));
     Criteria for the statement of the place of business (Sec.
201.1(i));
     Placement of the ingredient information required by
section 502(e) of the FFD&C Act (Sec.  201.10(a));
     Criteria for the statement of the percentage of an
ingredient in a drug (Sec.  201.10(d)(2));
     Declaration that an ingredient is a derivative or a
preparation of a substance specifically named in section 502(e) of the
FFD&C Act when the established name does not indicate such (Sec.
201.10(f));
     Criteria for the frequency of use and use in the running
text of the established name in association with the proprietary name
or designation for the drug or any ingredient thereof in the label or
labeling of a prescription drug (Sec.  201.10(g)(1));
     The placement of the quantitative ingredient information
when the established name does not correspond to the proprietary name
or designation and the prescription drug contains two or more active
ingredients (Sec.  201.10(h)(1));
     The location of the expiration date (Sec.  201.17);
     The information provided by the lot number (Sec.  201.18);
     Use of the term ``infant'' (Sec.  201.19);
     Declaration of the presence of FD&C Yellow No. 5 and FD&C
Yellow No. 6 in certain drugs for human use (Sec.  201.20);
     Declaration of the presence of phenylalanine as a
component of aspartame in over-the-counter and prescription drugs for
human use (Sec.  201.21);
     Required warning statements for prescription drugs
containing sulfites (Sec.  201.22);
     Labeling statements for systemic antibacterial drug
products (Sec.  201.24); and
     The prescribed statement for investigational new drugs
limiting them to investigational use (Sec.  312.6(a)).
2. Biological Drug Products (Sec.  610.68(f))
    In addition to the labeling requirements for investigational new
drugs in Sec.  312.6, certain labeling requirements for biological
products in 21 CFR part 610 subpart G, except to the extent that they
are explicitly required by statute, may also be the subject of an
exception or alternative under this rule:
     The information required on the product's container label
(Sec.  610.60);\2\
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    \2\This is distinct from the requirements for a product's
package label under Sec.  610.61 (21 CFR 610.61).
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     Certain information on the package label, specifically:
Lot number, information on the preservative, number of containers,
recommended storage temperature, certain instructions for use,
recommended individual dose, route of administration, known sensitizing
substances, type and amount of added antibiotics, inactive ingredients,
adjuvant, source of product, identity of microorganisms used in
manufacture, and minimum potency (Sec.  610.61(c) and (e) through (r));
     Requirements relating to the position and prominence of
the proper name on the package label as well as requirements relating
to size and type of characters (21 CFR 610.62);
     The placement on the container and package label of the
name, address, and license information of each manufacturer
participating in the manufacture of a biological product, if two or
more manufacturers participate in manufacturing (21 CFR 610.63);
     The name and address of the distributor, and the required
identifying phrases on the label (21 CFR 610.64); and
     Label requirements relating to products for export (21 CFR
610.65)
3. Medical Devices (Sec.  801.128(f))
    For medical devices, the appropriate FDA Center Director may grant
a request for an exception or alternative to certain labeling
requirements in parts 801 and 812 (21 CFR parts 801 and 812), except to
the extent that they are explicitly required by statute:
     Criteria for the statement of the place of business (Sec.
801.1(d));
     Labeling information on the principal display panel of
over-the-counter devices in package form, i.e., the part of a label
that is most likely to be displayed, presented, shown, or examined
under customary conditions of display for retail sale (Sec.  801.60);
     Requirements related to an accurate statement of principal
intended action and format of a statement of identity for an over-the-
counter device in package form (Sec.  801.61);
     Requirements related to the declaration of net quantity of
contents on the label of an over-the-counter device in package form
(Sec.  801.62);
     Warning statement for over-the-counter devices containing
or manufactured with chlorofluorocarbons and other class I ozone-
depleting substances (Sec.  801.63);
     Labeling requirements for prescription devices (Sec.
801.109);
     Labeling requirements for specific devices including
dentures and hearing aids (part 801, subpart H);
     The prescribed statement for investigational devices
limiting the device to investigational use (Sec.  812.5(a)); and
     The prescribed statement for investigational devices used
solely on research animals limiting the device to investigational use
in laboratory animals (Sec.  812.5(c)).
4. In Vitro Diagnostic Products (Sec.  809.11(f))
    The appropriate FDA Center Director may grant a request for an
exception or alternative to the following requirements pertaining to
IVDs in parts 809 (21 CFR part 809) and 812, except to the extent that
they are explicitly required by statute.
     Certain label information for IVDs, i.e., the proprietary
name; the intended use or uses of the product; for a reagent, the
declaration of the established name, if any, the quantity, proportion,
and concentration of each reactive ingredient, and the source and
activity if derived from a biological material; statement of warnings
or precautions; for a reagent, appropriate storage instructions
adequate to protect the stability of the product; for a reagent, a
means by which the user may be ensured that the product meets
appropriate standards of identity, strength, quality and purity at the
time of use; and a lot or control number (Sec.  809.10(a)(1) through
(a)(6) and (a)(9));

     Labeling accompanying each IVD, including reagents and
instruments, i.e., such information as proprietary name, intended use
or uses, summary and explanation of the test, a statement of warnings
or precautions for users, information regarding specimen collection and
preparation for analysis, outline of recommended procedures,
information regarding results, limitation of the procedure, expected
values, specific performance characteristics, and bibliography (Sec.
809.10(b));
     The prescribed statements for investigational IVDs that
are not subject to part 812 (Sec.  809.10(c)(2));
     The label of general purpose laboratory reagents, i.e.,
the proprietary name; the quantity, proportion, or concentration of the
reagent ingredient; and for a reagent derived from biological material,
the source and measure of activity; statement of purity and quality of
the reagent; statement of warnings or precautions; appropriate storage
instructions adequate to protect the stability of the product; and a
lot or control number (Sec.  809.10(d)(1)(i) through (d)(1)(v) and
(d)(1)(viii));
     Labeling of general purpose laboratory equipment, i.e.,
description of the product, its composition, and physical
characteristics if necessary for use (Sec.  809.10(d)(2)); and
     Labeling for analyte specific reagents, i.e., the
proprietary name; the quantity, proportion, or concentration of the
reagent ingredient; and for a reagent derived from biological material,
the source and measure of activity; statement of purity and quality of
the reagent; statement of warnings or precautions for users; date of
manufacture and appropriate storage instructions adequate to protect
the stability of the product; a lot or control number; prescribed
statements regarding analytical and performance characteristics
specific to class I, II, and III analyte specific reagents (Sec.
809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through (e)(1)(xi)).

IV. Legal Authority

    In this interim final rule, FDA is amending regulations pertaining
to the content and format of medical product labeling. The provisions
of this rule will allow FDA to grant exceptions or alternatives to
certain of those labeling requirements. The labeling regulations to
which exceptions or alternatives will be permitted were issued by FDA
under authority of the FFD&C Act and the PHS Act to mandate particular
ways that firms must satisfy the broad requirements and prohibitions in
those statutes, such as the prohibition on false and misleading drug
and device labeling. As described in section II of this document, FDA
has determined that circumstances may arise in which compliance with
those regulatory mandates could adversely affect the safety,
effectiveness, or availability of certain medical products that are or
will be included in the SNS. Moreover, due to the unique nature of the
SNS, those products could deviate from particular mandates of existing
labeling regulations without violating the broad statutory requirements
and prohibitions in the FFD&C Act and the PHS Act. For those reasons,
FDA is exercising its authority to regulate labeling by modifying the
existing regulations in a way that will allow exceptions or
alternatives for medical products that are or will be included in the
SNS.
    FDA has various sources of authority to issue labeling regulations.
For example, under section 502(a) of the FFD&C Act, a drug (including
biological products) or device is misbranded if its labeling is false
or misleading in any particular. In determining whether a product's
labeling is misleading, FDA may consider not only representations or
suggestions made in the labeling, but also whether the labeling fails
to reveal material facts in light of those representations or
suggestions or with respect to consequences which may result from the
use of the product under customary or usual conditions of use (section
201(n) of the FFD&C Act (21 U.S.C. 321(n))). By authority delegated
under section 701(a) of the FFD&C Act (21 U.S.C. 371(a)), FDA is
authorized to issue regulations for the efficient enforcement of the
FFD&C Act. Existing FDA regulations mandating specific labeling content
and format for drugs and devices satisfy those general statutory
standards. For example, many labeling regulations are designed to
ensure that nothing in the labeling is false or misleading in any
particular, to ensure that the labeling reveals all material facts in
light of the representations or suggestions in the labeling, and to
ensure that FDA may efficiently enforce those statutory requirements as
well as other requirements of the FFD&C Act and the PHS Act.
    Because biological products are also drugs as defined within the
FFD&C Act, the authority discussed previously extends to regulations
prescribing content and format requirements for biological product
labeling. There is, however, additional legal authority in the PHS Act
for this rule's requirements with respect to biological products
generally. For example, section 351(a)(1)(A) of the PHS Act provides
that no person may introduce or deliver for introduction into
interstate commerce any biological product unless a biologics license
is in effect for the product. By authority delegated under section
351(a)(2)(A) of the PHS Act, FDA is required to establish, by
regulation, requirements for the approval, suspension, and revocation
of biologics licenses.
    Because the SNS is intended ``to provide for the emergency health
security of the United States * * * in the event of a bioterrorist
attack or other public health emergency,''\3\ the SNS may contain
products that would otherwise not be available for widespread
distribution. For example, the ASPR (exercising the Secretary's
authority), in collaboration with the Director of the CDC and in
coordination with the Department of Homeland Security, may determine
that it is appropriate to include certain investigational medical
products in the SNS. As described in section II of this document, some
of these products require storage at extremely low temperatures and
cannot be temporarily removed from storage for relabeling without
compromising their integrity. Moreover, shipping products from SNS
storage sites to relabelers or back to manufacturers for relabeling
could increase the potential for sabotage and diversion, as well as
increase exposure to conditions affecting product quality, such as
temperature deviations. As a result, removing these investigational
products from storage for relabeling at the time of approval and then
returning them to storage could undermine their safety, effectiveness,
or availability and, in some cases, would be impracticable. Compliance
with the FDA regulations that would require such relabeling could
discourage SNS procurement of these products and thereby limit
available countermeasures in the event of a bioterrorist attack or
other public health emergency.
---------------------------------------------------------------------------

    \3\Section 3 of the Project BioShield Act of 2004 (section 319F-
2 of the PHS Act (42 U.S.C. 247d-6b)).
---------------------------------------------------------------------------

    To address this concern, FDA is creating a mechanism to allow
exceptions or alternatives to the labeling regulations specified in
this rule to help ensure the safety, effectiveness, and availability of
medical products that are or will be included in the SNS. FDA has
concluded that exceptions or alternatives granted under this rule will
not render products misbranded due to the additional safeguards and
conditions that may be required when an exception or alternative is
granted, as well as the unique storage, deployment, and distribution
considerations

essential to the SNS. As explained in section III.D of this document, a
grant of an exception or alternative under this rule may include
additional safeguards or conditions so that the labeling of products
subject to the exception or alternative includes information needed for
safe and effective use under the anticipated circumstances of use.
Moreover, products intended for use in certain public health
emergencies are likely to be administered to large numbers of people
within confined geographic areas, such as in the case of a natural
disaster. These SNS products may therefore be packaged in large
quantities to facilitate rapid distribution on extremely short notice.
Consequently, their packaging and distribution may differ from that of
non-SNS products. Moreover, HHS may establish special mechanisms to
provide product information, collect adverse event information, and
track the product's distribution.
    This rule does not create exemptions from express statutory
requirements or prohibitions regarding medical product labeling. The
FFD&C Act and the PHS Act set forth certain types of information that
must appear in the labeling for medical products. For example, section
351(a)(1)(B) of the PHS Act provides that each package of a biological
product must be marked with the proper name of the biological product;
the name, address, and applicable license number of the manufacturer of
the biological product; and the expiration date of the biological
product. Drugs (including biological products) and medical devices in
package form must bear labels containing the name and place of business
of the manufacturer, packer, or distributor (section 502(b)(1) of the
FFD&C Act). This interim final rule does not permit exceptions or
alternatives to any of those requirements. In addition, the FFD&C Act
and the PHS Act both prohibit false labeling (section 502(a) of the
FFD&C Act); section 351(b) of the PHS Act). This interim final rule
does not allow false information to appear in medical product labeling.
    As noted previously, this rule does not limit FDA's ability to
exercise enforcement discretion with respect to statutory and
regulatory requirements, including those involving medical product
labeling (see Heckler v. Chaney, 470 U.S. 821 (1985)).
    To the extent that a State requires labeling that directly
conflicts with, is different from, or is in addition, to any exceptions
or alternatives granted under this rule, the State-required labeling
would be subject to implied conflict preemption and, in some cases,
express preemption. FDA restated its longstanding views on preemption
in the preamble to the recently promulgated final rule entitled
``Requirements on Content and Format of Labeling for Human Prescription
Drug and Biological Products'' (see 71 FR 3922 at 3933 through 3936 and
3967 through 3969; January 24, 2006), and that discussion reflects the
agency's current position on this issue.
    Under the principles of implied conflict preemption, courts have
found State law preempted where it is impossible to comply with both
Federal and State law or where the State law ``stands as an obstacle to
the accomplishment and execution of the full purposes and objectives of
Congress.'' See English v. General Electric Co., 496 U.S. 72, 79
(1990); Florida Lime & Avocado Growers, Inc., 373 U.S. 132, 142-143
(1963); Hines v. Davidowitz, 312 U.S. 52, 67 (1941). Consistent with
this case law, section 4(a) of Executive Order 13132 states that
``[a]gencies shall construe * * * a Federal statute to preempt State
law only where the statute contains an express preemption provision or
there is some other clear evidence that the Congress intended
preemption of State law, or where the exercise of State authority
conflicts with the exercise of Federal authority under the Federal
statute.''
    As explained previously, this interim final rule will facilitate
the safety, effectiveness, and availability of appropriate medical
countermeasures in the event of a public health emergency. Because
Congress authorized the SNS to ``provide for the emergency health
security of the United States * * * in the event of a bioterrorist
attack or other public health emergency,'' products held in the SNS
should be ready for deployment at all times. In an emergency, it is
critical that State requirements regarding the content and format of
labeling do not interfere with the safety, effectiveness, or
availability of SNS products. FDA believes that State-required labeling
requirements different from or in addition to FDA requirements would
``stand as an obstacle to the accomplishment and execution of the full
purposes and objectives of Congress.'' See Hines, 312 U.S. at 67.
Moreover, these State requirements would ``conflict with the exercise
of Federal authority under [PHS Act section 319F-2, 42 U.S.C. 247d-
6b].'' See Executive Order 13132.
    Additionally, under section 751 of the FFD&C Act (21 U.S.C. 379r),
State or local requirements that are different from or in addition to
exceptions or alternatives granted under this rule, and relate to the
regulation of nonprescription drugs, are expressly preempted.
Similarly, in accordance with section 521 of the FFD&C Act (21 U.S.C.
360k), State or local requirements that are different from, or in
addition to, exceptions or alternatives granted under this rule with
respect to approved medical devices are expressly preempted. See the
Federalism section in this document for additional discussion of
preemption in the context of this interim final rule.

V. Issuance of an Interim Final Rule, Immediate Effective Date, and
Opportunity for Public Comment

    FDA is issuing this rule as an interim final rule, effective
immediately, with an opportunity for public comment. Section
553(b)(3)(B) of the Administrative Procedure Act (5 U.S.C.
553(b)(3)(B)) provides that, when an agency for good cause finds that
notice and public procedure are impracticable, unnecessary, or contrary
to public interest, the agency may issue a rule without providing
notice and public comment. FDA has determined that there is good cause
under 5 U.S.C. 553(b)(3)(B) and 21 CFR 10.40(d) to publish this
regulation as an interim final rule. An emergency requiring deployment
of medical products in the SNS could happen at any time. Without this
rule, the safety, effectiveness, or availability of medical products
held in the SNS could be adversely affected because of relabeling
requirements. An interim final rule ensures that a legal mechanism is
immediately available for addressing labeling issues associated with
medical products in the SNS without compromising their safety,
effectiveness, or availability for use in an emergency. Products held
in the SNS should be ready for deployment at all times.
    FDA invites public comment on this interim final rule. The comment
period on this interim final rule will be 90 days. The agency will
consider modifications to this interim final rule based on comments
made during the comment period. 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.

    FDA will address comments received and confirm or amend this
interim final rule in a final rule.

VI. Analysis of Impacts

    FDA has examined the impacts of the interim final rule under
Executive Order 12866, 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 a 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 of the deregulatory nature of this rule and
the minimal costs associated with applying for an exception or
alternative under this rule, the agency 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 proposing ``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 $127 million, using the most current (2006) 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.

A. Need for the Interim Final Rule

    FDA is issuing this interim final rule to allow for exceptions or
alternatives to specified labeling requirements for certain medical
products that are or will be in the SNS. As explained in other sections
of this preamble, compliance with these labeling requirements in some
circumstances could adversely affect or compromise the safety,
effectiveness or availability of these products. Exceptions or
alternatives to certain labeling requirements will provide the
flexibility needed to help ensure that FDA-regulated medical products
that are or will be in the SNS are not deemed misbranded and are
available in an emergency situation.

B. Scope of the Interim Final Rule

    This interim final rule applies to medical products that are or
will be stockpiled by the SNS. It allows entities that manufacture
(including labeling, packing, relabeling, or repackaging), distribute,
or store affected SNS products to request an exception or alternative
to specified regulatory labeling requirements for human drugs,
biological products, and medical devices to prevent misbranding of
those products in the SNS. Any grant of such a request by an FDA Center
Director would apply to specified lots, batches, or other units of
medical product identified in the request. When reviewing requests, the
FDA Center Director will consider whether complying with the specified
labeling regulations could adversely affect the safety, effectiveness,
or availability of stockpiled products and may impose appropriate
safeguards and conditions so that the labeling of products subject to
the request would include information needed for safe and effective use
under the anticipated circumstances of use. Alternatively, at his or
her own initiative, an FDA Center Director may grant an exception or
alternative to the specified labeling provisions without receiving a
written request. Allowing the agency the ability to act on its own
initiative could help avoid misbranding of products that are or will be
in the SNS.

C. Costs of the Interim Final Rule

    This rule would allow SNS officials and entities that manufacture
(including labeling, packing, relabeling, or repackaging), distribute,
or store medical products in the SNS to request exceptions from certain
labeling requirements in FDA regulations. An exception or alternative
from specified labeling requirements for FDA-regulated medical products
can also be initiated by the appropriate FDA Center Director. The
interim final rule would impose compliance costs on industry when
entities prepare and submit requests for exceptions or alternatives to
labeling requirements to avoid misbranding of their products that are
or will be in the SNS. However, granting exceptions or alternatives to
labeling requirements would provide the government with the flexibility
needed to more efficiently manage medical products in the SNS without
risking the availability of medical products for emergency use (see
section VI.D of this document, Benefits of the Interim Final Rule).
    FDA estimates that requests for exceptions would cost from $380 to
$1,130 for each request. Regulatory Affairs personnel may spend from 8
to 24 hours per request preparing the information that would be
required in an application for an exception or alternative under this
rule. According to Bureau of Labor Statistics data, the fully loaded
hourly wage for management and professional employees working in goods-
producing industries was $47.25 in 2004 (U.S. Department of Labor,
Bureau of Labor Statistics, ``Employer Cost Employee Compensation--
December 2004,'' Bureau of Labor Statistics News, USDL 05-432, March
16, 2005).

D. Benefits of the Interim Final Rule

    Although the agency has no data to quantify the benefits, this
interim final rule provides flexibility in labeling requirements for
FDA-regulated medical products in the SNS. If an exception or
alternative is granted, affected medical products in the SNS would not
be misbranded and would not be rendered unavailable for emergency use
due to relabeling operations. Exceptions or alternatives may be granted
on a case-by-case basis at the initiative of the appropriate FDA Center
Director or after receipt of a written request from an entity that
manufactures, distributes, or stores products in the SNS. To illustrate
the potential benefits of this rule we describe costs that could be
avoided by granting an exception or alternative to certain labeling
requirements upon written request of a manufacturer.
    In some cases, granting an exception to labeling requirements may
save direct relabeling costs. For example, to change information on a
carton or container label, a firm might spend $300 in material costs
for new artwork, $600 to $1,000 in labor costs to prepare the new
artwork and about 10 cents to print each new carton or container label.
Besides the costs to prepare a new carton, there would be additional
labor costs to remove the product from the old carton and insert it in
the new carton. With a container label, it is likely that the new label
could be affixed directly on top of the existing label, reducing the
amount of effort needed to make this change. Because packaging is
normally automated, the agency has no information about how much time
it would take to manually replace a container label or exchange a
carton, but believes this could cost about 5 to 10 cents per unit.
    Before the implementation of this rule, when an investigational
product in

the SNS was subsequently approved, the product labeling would have
needed to be immediately changed to add approved labeling information
that was unavailable prior to approval. An exception or alternative to
these labeling requirements might allow entities to ship
investigational products with labeling that can be manually modified or
supplemented at the SNS location once the drug is approved. Without an
exception or alternative, it would be necessary to remove the
investigational products from the SNS for relabeling or, in some cases,
to replace the product.
    This rule would avoid other potential costs. Without an exception
or alternative, the SNS might be required to purchase costly
replacement units. In other cases, some products may be appropriate for
exceptions or alternatives because their availability for use in an
emergency could be compromised if they had to be shipped out of the SNS
to be relabeled. Removing such products from the stockpile, even
temporarily, could jeopardize or adversely affect product safety or
effectiveness (due to conditions of relabeling or related shipping,
storage, and handling), requiring additional product testing or product
replacement. Because replacement costs would vary widely and depend on
the nature of the product, the number of units affected, and current
market price, the amount of these avoided costs is unknown.
    Although we only describe the potential benefits of this interim
final rule in qualitative terms, we believe it is reasonable to assume
that the benefits of providing flexibility in labeling requirements for
SNS products justify the potential compliance costs of the rule.
Moreover, the rule will allow FDA the flexibility to manage the
products in the SNS without risking the safety, effectiveness, or
availability of these products for use in an emergency.

E. Small Business Impacts

    FDA has examined the economic implications of this proposed rule as
required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a
rule has a significant economic impact on a substantial number of small
entities, the Regulatory Flexibility Act requires agencies to analyze
regulatory options that would lessen the economic effect of the rule on
small entities. This rule is not expected to have a significant impact
on a substantial number of small entities. It is estimated that this
interim final rule will cost small entities no more than $1,130 when
they submit a request. For affected small entities (e.g., medical
product manufacturers, relabelers, or packers) we expect that this
would represent a negligible proportion of annual receipts. Therefore,
the agency certifies that the interim final rule will not have a
significant economic impact on a substantial number of small entities.

F. Regulatory Options Considered

    No new regulatory action. The agency considered and rejected this
option. The Agency recognized that certain medical products in the SNS,
due to their anticipated circumstances of use in an emergency, might
need to be labeled in a manner that did not comply with certain FDA
labeling regulations. Without the ability to grant an exception to
labeling requirements, existing FDA labeling regulations would have
rendered such medical products misbranded. Moreover, the relabeling of
these products to comply with FDA labeling regulations could have
adversely affected their safety, effectiveness, or availability. As a
result, FDA would have needed to exercise enforcement discretion to
allow labeling to deviate from FDA requirements. To the extent
possible, FDA believes that amending its labeling regulations is
preferable to reliance on enforcement discretion to ensure the
continued availability of medical products that are or will be in the
SNS.

VII. The Paperwork Reduction Act of 1995

    This interim final rule contains information collection provisions
that are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). The title, description, and respondent description of the
information collection provisions are shown as follows with an estimate
of the annual reporting burden. Included in the estimate is the time
for reviewing instructions, searching existing data sources, gathering
and maintaining the data needed, and completing and reviewing each
collection of information.
    FDA invites comments on the following topics: (1) Whether the
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
collection of information, including the validity of the methodology
and assumptions used; (3) ways to enhance the quality, utility, and
clarity of the information to be collected; and (4) ways to minimize
the burden of the collection of information on respondents, including
through the use of automated collection techniques, when appropriate,
and other forms of information technology.
    Title: Exceptions or Alternatives to Labeling Requirements for
Products Held by the Strategic National Stockpile.
    Description: FDA is issuing regulations to permit FDA Center
Directors to grant a request submitted under Sec. Sec.  201.26(c)(1)(i)
(human drug products), 610.68(c)(1)(i) (biological products),
801.128(c)(1)(i) (medical devices), and 809.11(c)(1)(i) (in vitro
diagnostic products for human use) for an exception or alternative to
certain applicable regulatory labeling provisions when these products
are or will be included in the SNS.
    The request must:
     Identify the specified lots, batches, or other units of
the affected product;
     Identify the labeling provisions under this rule that are
the subject of the request;
     Explain why compliance with the specified labeling
provisions could adversely affect the safety, effectiveness, or
availability of the product subject to the request;
     Describe any proposed safeguards or conditions that will
be implemented so that the labeling of the product includes appropriate
information necessary for the safe and effective use of the product
given the anticipated circumstances of use of the product;
     Provide a draft of the proposed labeling; and
     Provide any other information requested by the FDA Center
Director in support of the request.
    The FDA Center Director will grant the request if he or she
determines that compliance with the identified labeling provisions
could adversely affect the safety, effectiveness, or availability of
specified lots, batches, or other units of human drugs, biological
products, or medical devices that are or will be included in the SNS.
    Description of Respondents: Entities that manufacture (including
labeling, packing, relabeling, or repackaging), distribute, or store
affected products.
    FDA estimates the information collection burden 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
--------------------------------------------------------------------------------------------------------------------------------------------------------
201.26(c)(1)(i)                                                        18                     1                 18                 24                432
--------------------------------------------------------------------------------------------------------------------------------------------------------
610.68(c)(1)(i)                                                        10                     1                 10                 24                240
--------------------------------------------------------------------------------------------------------------------------------------------------------
801.128(c)(1)(i) and 809.11(c)(1)(i)                                    2                     1                  2                 24                 48
--------------------------------------------------------------------------------------------------------------------------------------------------------
Total                                                                                720
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\There are no capital costs or operating and maintenance costs associated with this collection of information.

    Although FDA cannot predict the number of future requests, based on
limited information within FDA, we estimate that approximately 30
respondents will request annually one exception or alternative to
labeling provisions to avoid misbranding of their products in the SNS.
The estimate of one request per respondent is based on the anticipated
occasional occurrence of a product being misbranded while in the SNS.
We are estimating that each respondent will spend from 8 to 24 hours
preparing each request. The hours per response are based on estimated
time that it takes to prepare a supplement to an application, which may
be considered similar to a request for an exception or alternative.
    The information collection provisions in Sec. Sec.  314.70, 601.12,
807.81 and 814.39 have been approved under OMB control numbers 0910-
0001 (expires May 31, 2008), 0910-0338 (expires September 30, 2008),
0910-0120 (expires August 31, 2010), and 0910-0231 (expires September
30, 2007), respectively.
    The information collection provisions for this interim final rule
have been approved under the emergency processing provisions of the
PRA. The assigned OMB approval number of this collection of information
is 0910-0614. This approval expires on June 30, 2008. Interested
persons are requested to fax comments regarding the information
collection by (see DATES) to the Office of Information and Regulatory
Affairs, OMB (see ADDRESSES).
    An agency may not conduct or sponsor, and a person is not required
to respond to, a collection of information unless it displays a
currently valid OMB control number.

VIII. Environmental Impact

    The agency has determined under 21 CFR 25.30(k) 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.

IX. Federalism

    As stated in the preamble, FDA has analyzed this interim final rule
in accordance with the principles set forth in Executive Order 13132.
Section 4(a) of this Executive Order requires agencies to ``construe *
* * a Federal statute to preempt State law only where the statute
contains an express preemption provision or there is some other clear
evidence that the Congress intended preemption of State law, or where
the exercise of State authority conflicts with the exercise of Federal
authority under the Federal statute.'' In this rule, FDA is revising
certain requirements concerning the format and content of labeling for
human drugs, biological products, and medical devices that are or will
be included in the SNS to provide for exceptions or alternatives to
these requirements under specified circumstances. To the extent that a
State requires labeling that directly conflicts with, is different
from, or is in addition, to any exceptions or alternatives granted
under this rule, the State-required labeling would be subject to
implied conflict preemption. Moreover, certain State requirements
regarding the format and content of nonprescription drug labeling and/
or labeling of approved medical devices may be subject to the express
preemption provisions in section 751 of the FFD&C Act (21 U.S.C. 360k)
(nonprescription drugs) and section 521 of the FFD&C Act (approved
medical devices).
    FDA is aware that State requirements on medical product labeling,
often as a result of product liability lawsuits, may conflict with
Federal requirements. FDA restated its longstanding views on preemption
in the preamble to the recently promulgated final rule entitled
``Requirements on Content and Format of Labeling for Human Prescription
Drug and Biological Products'' (see 71 FR 3922 at 3933 through 3936 and
3967 through 3969). That discussion is applicable to this interim final
rule as well, and reflects the agency's current position on this issue.
    Section 4(c) of Executive Order 13132 instructs us to restrict any
Federal preemption of State law to the ``minimum level necessary to
achieve the objectives of the statute pursuant to which the regulations
are promulgated.'' This interim final rule meets the preceding
requirement because, as discussed previously, it would preempt only
State laws that directly conflict with, are different from, or are in
addition to any Federal requirements. Section 4(d) of Executive Order
13132 states that when an agency foresees the possibility of a conflict
between State law and federally protected interests within the agency's
area of regulatory responsibility, the agency ``shall consult, to the
extent practicable, with appropriate State and local officials in an
effort to avoid such a conflict.'' In this case, FDA foresees the
possibility of a conflict between State law and federally protected
interests within the agency's area of regulatory responsibility.
    Section 4(e) of Executive Order 13132 adds that ``when an agency
proposes to act through adjudication or rulemaking to preempt State
law, the agency ``shall provide all affected State and local officials
notice and an opportunity for appropriate participation in the
proceedings.'' FDA is seeking input from all stakeholders on the
provisions of this interim final rule through publication of the rule
in the Federal Register, and will consult with State and local
officials in an effort to avoid conflicts between State law and Federal
protected interests in accordance with Executive Order 13132.
    In conclusion, the agency believes that it has complied with all of
the applicable requirements under Executive Order 13132 and has
determined that this interim final rule is consistent with the
Executive order.

X. Request for Comments

    Interested persons may submit to the Division of Dockets Management
(see

ADDRESSES) written or electronic comments regarding this document.
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

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 312

    Drugs, Exports, Imports, Investigations, Labeling, Medical
research, Reporting and recordkeeping requirements, Safety.

21 CFR Part 314

    Administrative practice and procedure, Confidential business
information, Drugs, Reporting and recordkeeping requirements.

21 CFR Part 601

    Administrative practice and procedure, Biologics, Confidential
business information.

21 CFR Part 610

    Biologics, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 801

    Labeling, Medical devices, Reporting and recordkeeping
requirements.

21 CFR Part 807

    Confidential business information, Imports, Medical devices,
Reporting and recordkeeping requirements.

21 CFR Part 809

    Labeling, Medical devices.

21 CFR Part 812

    Health records, Medical devices, Medical research, Reporting and
recordkeeping requirements.

21 CFR Part 814

    Administrative practice and procedure, Confidential business
information, Medical devices, Medical research, Reporting and
recordkeeping requirements.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and the
Public Health Service Act, and under authority delegated to the
Commissioner of Food and Drugs, 21 CFR chapter I is amended as follows:

PART 201--LABELING

0
1. The authority citation for 21 CFR part 201 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360,
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

0
2. Add Sec.  201.26 to subpart A to read as follows:

Sec.  201.26  Exceptions or alternatives to labeling requirements for
human drug products held by the Strategic National Stockpile.

    (a) The appropriate FDA Center Director may grant an exception or
alternative to any provision listed in paragraph (f) of this section
and not explicitly required by statute, for specified lots, batches, or
other units of a human drug product, if the Center Director determines
that compliance with such labeling requirement could adversely affect
the safety, effectiveness, or availability of such product that is or
will be included in the Strategic National Stockpile.
    (b)(1)(i) A Strategic National Stockpile official or any entity
that manufactures (including labeling, packing, relabeling, or
repackaging), distributes, or stores a human drug product that is or
will be included in the Strategic National Stockpile may submit, with
written concurrence from a Strategic National Stockpile official, a
written request for an exception or alternative described in paragraph
(a) of this section to the Center Director.
    (ii) The Center Director may grant an exception or alternative
described in paragraph (a) of this section on his or her own
initiative.
    (2) A written request for an exception or alternative described in
paragraph (a) of this section must:
    (i) Identify the specified lots, batches, or other units of the
human drug product that would be subject to the exception or
alternative;
    (ii) Identify the labeling provision(s) listed in paragraph (f) of
this section that are the subject of the exception or alternative
request;
    (iii) Explain why compliance with such labeling provision(s) could
adversely affect the safety, effectiveness, or availability of the
specified lots, batches, or other units of a human drug product that
are or will be held in the Strategic National Stockpile;
    (iv) Describe any proposed safeguards or conditions that will be
implemented so that the labeling of the product includes appropriate
information necessary for the safe and effective use of the product,
given the anticipated circumstances of use of the product;
    (v) Provide a draft of the proposed labeling of the specified lots,
batches, or other units of the human drug product subject to the
exception or alternative; and
    (vi) Provide any other information requested by the Center Director
in support of the request.
    (c) The Center Director must respond in writing to all requests
under this section.
    (d) A grant of an exception or alternative under this section will
include any safeguards or conditions deemed appropriate by the Center
Director so that the labeling of product subject to the exception or
alternative includes the information necessary for the safe and
effective use of the product, given the anticipated circumstances of
use.
    (e) If you are a sponsor receiving a grant of a request for an
exception or alternative to the labeling requirements under this
section:
    (1) You need not submit a supplement under Sec.  314.70(a) through
(c) or Sec.  601.12(f)(1) through (f)(2) of this chapter; however,
    (2) You must report any grant of a request for an exception or
alternative under this section as part of your annual report under
Sec. Sec.  314.70(d) or 601.12(f)(3) of this chapter.
    (f) The Center Director may grant an exception or alternative under
this section to the following provisions of this chapter, to the extent
that the requirements in these provisions are not explicitly required
by statute:
    (1) Sec.  201.1(h)(1) through (h)(2), (h)(5) through (h)(6), and
(i);
    (2) Sec.  201.10(a), (d)(2), (f), (g)(1), and (h)(1);
    (3) Sec.  201.17;
    (4) Sec.  201.18;
    (5) Sec.  201.19;
    (6) Sec.  201.20;
    (7) Sec.  201.21;
    (8) Sec.  201.22;
    (9) Sec.  201.24; and
    (10) Sec.  312.6.

PART 312--INVESTIGATIONAL NEW DRUG APPLICATION

0
3. The authority citation for 21 CFR part 312 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 371,
381, 382, 383, 393; 42 U.S.C. 262.

0
4. Section 312.6 is amended by adding paragraph (c) to read as follows:

Sec.  312.6  Labeling of an investigational new drug.

* * * * *
    (c) The appropriate FDA Center Director, according to the
procedures set

forth in Sec. Sec.  201.26 or 610.68 of this chapter, may grant an
exception or alternative to the provision in paragraph (a) of this
section, to the extent that this provision is not explicitly required
by statute, for specified lots, batches, or other units of a human drug
product that is or will be included in the Strategic National
Stockpile.

PART 314--APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

0
5. The authority citation for 21 CFR part 314 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 355a, 356,
356a, 356b, 356c, 371, 374, 379e.

0
6. Section 314.70 is amended by revising paragraph (a)(1) to read as
follows:

Sec.  314.70  Supplements and other changes to an approved application.

    (a) * * *
    (1)(i) Except as provided in paragraph (a)(1)(ii) of this section,
the applicant must notify FDA about each change in each condition
established in an approved application beyond the variations already
provided for in the application. The notice is required to describe the
change fully. Depending on the type of change, the applicant must
notify FDA about the change in a supplement under paragraph (b) or (c)
of this section or by inclusion of the information in the annual report
to the application under paragraph (d) of this section.
    (ii) The submission and grant of a written request for an exception
or alternative under Sec.  201.26 of this chapter satisfies the
applicable requirements in paragraphs (a) through (c) of this section.
However, any grant of a request for an exception or alternative under
Sec.  201.26 of this chapter must be reported as part of the annual
report to the application under paragraph (d) of this section.
* * * * *

PART 601--LICENSING

0
7. The authority citation for 21 CFR part 601 continues to read as
follows:

    Authority: 15 U.S.C. 1451-1561; 21 U.S.C. 321, 351, 352, 353,
355, 356b, 360, 360c-360f, 360h-360j, 371, 374, 379e, 381; 42 U.S.C.
216, 241, 262, 263, 264; sec 122, Pub. L. 105-115, 111 Stat. 2322
(21 U.S.C. 355 note).

0
8. Section 601.12 is amended by revising paragraph (f)(3)(i)(D) and by
adding paragraph (f)(5) to read as follows:

Sec.  601.12  Changes to an approved application.

* * * * *
    (f) * * *
    (3)(i) * * *
    (D) A change made pursuant to an exception or alternative granted
under Sec.  201.26 or Sec.  610.68 of this chapter.
* * * * *
    (5) The submission and grant of a written request for an exception
or alternative under Sec.  201.26 or Sec.  610.68 of this chapter
satisfies the requirements in paragraphs (f)(1) through (f)(2) of this
section.
* * * * *

PART 610--GENERAL BIOLOGICAL PRODUCTS STANDARDS

0
9. The authority citation for 21 CFR part 610 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360c,
360d, 360h, 360i, 371, 372, 374, 381; 42 U.S.C. 216, 262, 263, 263a,
264.

0
10. Add Sec.  610.68 to subpart G to read as follows:

Sec.  610.68  Exceptions or alternatives to labeling requirements for
biological products held by the Strategic National Stockpile.

    (a) The appropriate FDA Center Director may grant an exception or
alternative to any provision listed in paragraph (f) of this section
and not explicitly required by statute, for specified lots, batches, or
other units of a biological product, if the Center Director determines
that compliance with such labeling requirement could adversely affect
the safety, effectiveness, or availability of such product that is or
will be included in the Strategic National Stockpile.
    (b)(1)(i) A Strategic National Stockpile official or any entity
that manufactures (including labeling, packing, relabeling, or
repackaging), distributes, or stores a biological product that is or
will be included in the Strategic National Stockpile may submit, with
written concurrence from a Strategic National Stockpile official, a
written request for an exception or alternative described in paragraph
(a) of this section to the Center Director.
    (ii) The Center Director may grant an exception or alternative
described in paragraph (a) of this section on his or her own
initiative.
    (2) A written request for an exception or alternative described in
paragraph (a) of this section must:
    (i) Identify the specified lots, batches, or other units of the
biological product that would be subject to the exception or
alternative;
    (ii) Identify the labeling provision(s) listed in paragraph (f) of
this section that are the subject of the exception or alternative
request;
    (iii) Explain why compliance with such labeling provision(s) could
adversely affect the safety, effectiveness, or availability of the
specified lots, batches, or other units of the biological product that
are or will be included in the Strategic National Stockpile;
    (iv) Describe any proposed safeguards or conditions that will be
implemented so that the labeling of the product includes appropriate
information necessary for the safe and effective use of the product,
given the anticipated circumstances of use of the product;
    (v) Provide a draft of the proposed labeling of the specified lots,
batches, or other units of the biological product subject to the
exception or alternative; and
    (vi) Provide any other information requested by the Center Director
in support of the request.
    (c) The Center Director must respond in writing to all requests
under this section.
    (d) A grant of an exception or alternative under this section will
include any safeguards or conditions deemed appropriate by the Center
Director so that the labeling of product subject to the exception or
alternative includes the information necessary for the safe and
effective use of the product, given the anticipated circumstances of
use.
    (e) If you are a sponsor receiving a grant of a request for an
exception or alternative to the labeling requirements under this
section:
    (1) You need not submit a supplement under Sec.  601.12(f)(1)
through (f)(2) of this chapter; however,
    (2) You must report any grant of a request for an exception or
alternative under this section as part of your annual report under
Sec.  601.12(f)(3) of this chapter.
    (f) The Center Director may grant an exception or alternative under
this section to the following provisions of this chapter, to the extent
that the requirements in these provisions are not explicitly required
by statute:
    (1) Sec.  610.60;
    (2) Sec.  610.61(c) and (e) through (r);
    (3) Sec.  610.62;
    (4) Sec.  610.63;
    (5) Sec.  610.64;
    (6) Sec.  610.65; and
    (7) Sec.  312.6.

PART 801--LABELING

0
11. The authority citation for 21 CFR part 801 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 360i, 360j, 371, 374.

0
12. Add Sec.  801.128 to subpart D to read as follows:

Sec.  801.128  Exceptions or alternatives to labeling requirements for
medical devices held by the Strategic National Stockpile.

    (a) The appropriate FDA Center Director may grant an exception or
alternative to any provision listed in paragraph (f) of this section
and not explicitly required by statute, for specified lots, batches, or
other units of a medical device, if the Center Director determines that
compliance with such labeling requirement could adversely affect the
safety, effectiveness, or availability of such devices that are or will
be included in the Strategic National Stockpile.
    (b)(1)(i) A Strategic National Stockpile official or any entity
that manufactures (including labeling, packing, relabeling, or
repackaging), distributes, or stores devices that are or will be
included in the Strategic National Stockpile may submit, with written
concurrence from a Strategic National Stockpile official, a written
request for an exception or alternative described in paragraph (a) of
this section to the Center Director.
    (ii) The Center Director may grant an exception or alternative
described in paragraph (a) of this section on his or her own
initiative.
    (2) A written request for an exception or alternative described in
paragraph (a) of this section must:
    (i) Identify the specified lots, batches, or other units of the
medical device that would be subject to the exception or alternative;
    (ii) Identify the labeling provision(s) listed in paragraph (f) of
this section that are the subject of the exception or alternative
request;
    (iii) Explain why compliance with the labeling provision(s) could
adversely affect the safety, effectiveness, or availability of the
specified lots, batches, or other units of a medical device that are or
will be held in the Strategic National Stockpile;
    (iv) Describe any proposed safeguards or conditions that will be
implemented so that the labeling of the device includes appropriate
information necessary for the safe and effective use of the device,
given the anticipated circumstances of use of the device;
    (v) Provide a draft of the proposed labeling of the specified lots,
batches, or other units of the medical device subject to the exception
or alternative; and
    (vi) Provide any other information requested by the Center Director
in support of the request.
    (c) The Center Director must respond in writing to all requests
under this section. The Center Director may impose appropriate
conditions when granting such an exception or alternative under this
section.
    (d) A grant of an exception or alternative under this section will
include any safeguards or conditions deemed appropriate by the Center
Director so that the labeling of devices subject to the exception or
alternative includes the information necessary for the safe and
effective use of the device, given the anticipated circumstances of
use.
    (e) If the Center Director grants a request for an exception or
alternative to the labeling requirements under this section:
    (1) The Center Director may determine that the submission and grant
of a written request under this section satisfies the provisions
relating to premarket notification submissions under Sec.  807.81(a)(3)
of this chapter.
    (2)(i) For a Premarket Approval Application (PMA)-approved device,
the submission and grant of a written request under this section
satisfies the provisions relating to submission of PMA supplements
under Sec.  814.39 of this chapter; however,
    (ii) The grant of the request must be identified in a periodic
report under Sec.  814.84 of this chapter.
    (f) The Center Director may grant an exception or alternative under
this section to the following provisions of this chapter, to the extent
that the requirements in these provisions are not explicitly required
by statute:
    (1) Sec.  801.1(d);
    (2) Sec.  801.60;
    (3) Sec.  801.61;
    (4) Sec.  801.62;
    (5) Sec.  801.63;
    (6) Sec.  801.109; and
    (7) Part 801, subpart H.

PART 807--ESTABLISHMENT REGISTRATION AND DEVICE LISTING FOR
MANUFACTURERS AND INITIAL IMPORTERS OF DEVICES

0
13. The authority citation for 21 CFR part 807 continues to read as
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 360, 360c, 360e, 360i,
360j, 371, 374, 381, 393; 42 U.S.C. 264, 271.

0
14. Section 807.81 is amended by revising paragraph (b) to read as
follows:

Sec.  807.81  When a premarket notification submission is required.

* * * * *
    (b)(1) A premarket notification under this subpart is not required
for a device for which a premarket approval application under section
515 of the act, or for which a petition to reclassify under section
513(f)(2) of the act, is pending before the Food and Drug
Administration.
    (2) The appropriate FDA Center Director may determine that the
submission and grant of a written request for an exception or
alternative under Sec.  801.128 or Sec.  809.11 of this chapter
satisfies the requirement in paragraph (a)(3) of this section.
* * * * *

PART 809--IN VITRO DIAGNOSTIC PRODUCTS FOR HUMAN USE

0
15. The authority citation for 21 CFR part 809 continues to read as
follows:

    Authority: 21 U.S.C. 331, 351, 352, 355, 360b, 360c, 360d, 360h,
360i, 360j, 371, 372, 374, 381.

0
16. Add Sec.  809.11 to subpart B to read as follows:

Sec.  809.11  Exceptions or alternatives to labeling requirements for
in vitro diagnostic products for human use held by the Strategic
National Stockpile.

    (a) The appropriate FDA Center Director may grant an exception or
alternative to any provision listed in paragraph (f) of this section
and not explicitly required by statute, for specified lots, batches, or
other units of an in vitro diagnostic product for human use, if the
Center Director determines that compliance with such labeling
requirement could adversely affect the safety, effectiveness, or
availability of such products that are or will be included in the
Strategic National Stockpile.
    (b)(1)(i) A Strategic National Stockpile official or any entity
that manufactures (including labeling, packing, relabeling, or
repackaging), distributes, or stores an in vitro diagnostic product for
human use that is or will be included in the Strategic National
Stockpile may submit, with written concurrence from a Strategic
National Stockpile official, a written request for an exception or
alternative described in paragraph (a) of this section to the Center
Director.
    (ii) The Center Director may grant an exception or alternative
described in paragraph (a) of this section on his or her own
initiative.
    (2) A written request for an exception or alternative described in
paragraph (a) of this section must:
    (i) Identify the specified lots, batches, or other units of an in
vitro diagnostic product for human use that would be subject to the
exception or alternative;
    (ii) Identify the labeling provision(s) listed in paragraph (f) of
this section that are the subject of the exception or alternative
request;
    (iii) Explain why compliance with such labeling provision(s) could

adversely affect the safety, effectiveness, or availability of the
specified lots, batches, or other units of the in vitro diagnostic
product for human use that are or will be held in the Strategic
National Stockpile;
    (iv) Describe any proposed safeguards or conditions that will be
implemented so that the labeling of the product includes appropriate
information necessary for the safe and effective use of the product,
given the anticipated circumstances of use of the product;
    (v) Provide a draft of the proposed labeling of the specified lots,
batches, or other units of the in vitro diagnostic products for human
use subject to the exception or alternative; and
    (vi) Provide any other information requested by the Center Director
in support of the request.
    (c) The Center Director must respond in writing to all requests
under this section. The Center Director may impose appropriate
conditions or safeguards when granting such an exception or alternative
under this section.
    (d) A grant of an exception or alternative under this section will
include any safeguards or conditions deemed appropriate by the Center
Director to ensure that the labeling of the product subject to the
exception or alternative includes the information necessary for the
safe and effective use of the product, given the anticipated
circumstances of use.
    (e) If the Center Director grants a request for an exception or
alternative to the labeling requirements under this section:
    (1) The Center Director may determine that the submission and grant
of a written request under this section satisfies the provisions
relating to premarket notification submissions under Sec.  807.81(a)(3)
of this chapter.
    (2)(i) For a Premarket Approval Application (PMA)-approved in vitro
diagnostic product for human use, the submission and grant of a written
request under this section satisfies the provisions relating to
submission of PMA supplements under Sec.  814.39 of this chapter;
however,
    (ii) The grant of the request must be identified in a periodic
report under Sec.  814.84 of this chapter.
    (f) The Center Director may grant an exception or alternative under
this section to the following provisions of this part, to the extent
that the requirements in these provisions are not explicitly required
by statute:
    (1) Sec.  809.10(a)(1) through (a)(6) and (a)(9);
    (2) Sec.  809.10(b);
    (3) Sec.  809.10(c)(2);
    (4) Sec.  809.10(d)(1)(i) through (d)(1)(v), (d)(1)(viii), and
(d)(2); and
    (5) Sec.  809.10(e)(1)(i) through (e)(1)(vi) and (e)(1)(ix) through
(e)(1)(xi).

PART 812--INVESTIGATIONAL DEVICE EXEMPTIONS

0
17. The authority citation for 21 CFR part 812 continues to read as
follows:

    Authority: 21 U.S.C. 331, 351, 352, 353, 355, 360, 360c-360f,
360h-360j, 371, 372, 374, 379e, 381, 382, 383; 42 U.S.C. 216, 241,
262, 263b-263n.

0
18. Section 812.5 is amended by adding paragraph (d) to read as
follows:

Sec.  812.5  Labeling of investigational devices.

* * * * *
    (d) The appropriate FDA Center Director, according to the
procedures set forth in Sec.  801.128 or Sec.  809.11 of this chapter,
may grant an exception or alternative to the provisions in paragraphs
(a) and (c) of this section, to the extent that these provisions are
not explicitly required by statute, for specified lots, batches, or
other units of a device that are or will be included in the Strategic
National Stockpile.

PART 814--PREMARKET APPROVAL OF MEDICAL DEVICES

0
19. The authority citation for 21 CFR part 814 continues to read as
follows:

    Authority: 21 U.S.C. 351, 352, 353, 360, 360c-360j, 371, 372,
373, 374, 375, 379, 379e, 381.

0
20. Section 814.39 is amended by adding paragraph (g) to read as
follows:

Sec.  814.39  PMA Supplements.

* * * * *
    (g) The submission and grant of a written request for an exception
or alternative under Sec.  801.128 or Sec.  809.11 of this chapter
satisfies the requirement in paragraph (a) of this section.

0
21. Section 814.84 is amended by adding paragraph (b)(3) to read as
follows:

Sec.  814.84  Reports.

* * * * *
    (b) * * *
    (3) Identify changes made pursuant to an exception or alternative
granted under Sec.  801.128 or Sec.  809.11 of this chapter.

    Dated: December 20, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-25165 Filed 12-27-07; 8:45 am]

BILLING CODE 4160-01-S