[Federal Register Volume 77, Number 24 (Monday, February 6, 2012)]
[Rules and Regulations]
[Pages 5696-5699]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2012-2558]
[[Page 5696]]
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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. FDA-2006-N-0364]
Exceptions or Alternatives to Labeling Requirements for Products
Held by the Strategic National Stockpile
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is adopting as a final
rule, without change, the interim final rule that issued regulations
permitting 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). FDA is taking this action to
complete the rulemaking initiated with the interim final rule.
DATES: This rule is effective February 6, 2012.
FOR FURTHER INFORMATION CONTACT:
For information concerning biological products:
Melissa Reisman, Center for Biologics Evaluation and Research (HFM-17),
Food and Drug Administration, 1401 Rockville Pike, suite 200N,
Rockville, MD 20852-1448, (301) 827-6210.
For information concerning drug products:
Brad G. Leissa, Center for Drug Evaluation and Research, Food and Drug
Administration, 10001 New Hampshire Ave., Hillandale Building, rm.
2170, Silver Spring, MD 20993, (301) 796-1693.
For information concerning medical devices:
Larry Spears, Center for Devices and Radiological Health, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 66, rm. 3412, Silver
Spring, MD 20993, (301) 796-5517.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of December 28, 2007 (72 FR 73589), FDA
issued an interim final rule entitled ``Exceptions or Alternatives to
Labeling Requirements for Products Held by the Strategic National
Stockpile'' (hereinafter referred to as the interim final rule).\1\
This rule became effective upon the date of publication in the Federal
Register.
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\1\ In the Federal Register of November 18, 2008 (73 FR 68332),
FDA issued a technical amendment to reincorporate a regulation that
was inadvertently revised by the interim final rule.
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We issued the interim final rule to facilitate the safety,
effectiveness, and availability of appropriate medical countermeasures
stored in the SNS in the event of a public health emergency. We also
recognized that it may be appropriate for certain human drugs,
biological products, or medical devices (hereinafter referred to
collectively as 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 requirements. However, noncompliance with these labeling
requirements could render such products misbranded under section 502 of
the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C.
352). Under this rule, the appropriate FDA Center Director may grant
exceptions or alternatives to certain regulatory labeling requirements
applicable to medical products that are or will be included in the SNS
if he or she determines that compliance with the labeling requirements
could adversely affect the safety, effectiveness, or availability of
specified lots, batches, or other units of medical products that are or
will be included in the SNS. An exception or alternative granted under
this rule may include conditions or safeguards deemed appropriate by
the FDA Center Director to ensure that the labeling for such products
includes information necessary for the safe and effective use of the
product given the product's anticipated circumstances of use.
For example, this rule applies to certain medical products that
enter the SNS as investigational products in addition to medical
products in the SNS that are approved, licensed, or cleared for
marketing.\2\ Labels on investigational products ordinarily would not
contain all elements required on licensed, approved, or cleared product
labels. Certain information, such as expiration dates, warnings for
users, license numbers of manufacturers and other information, may not
be available or finalized for an investigational product, and thus
could not be included on a container label if the investigational
product was added to the SNS. Prior to the implementation of this rule,
when investigational products were ultimately approved for marketing,
the products would have been returned to the manufacturer or sent to
relabelers for relabeling, a potentially time-consuming, costly, and
labor-intensive process. Further, requiring relabeling of such
investigational products after approval, licensure or clearance could
adversely affect the safety, effectiveness, or availability of the
products. This rule allows the appropriate FDA Center Director to grant
an exception or alternative to the relevant labeling requirements to
enable the immediate use of a product in the event of a public health
emergency.
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\2\ As noted in the preamble to the interim final rule, medical
products stockpiled in the SNS may also include products that will
ultimately be used in an emergency under section 564 of the FD&C Act
(21 U.S.C. 360bbb-3).
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For these reasons, as explained in the interim final rule and 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.
II. Comments on the Interim Final Rule and FDA Responses
We received 7 comments on the proposed rule. These comments were
received from hospitals, biologics manufacturers, law firms, other
government agencies, and other interested persons. To make it easier to
identify comments and our responses, the word ``Comment,'' in
parentheses, will appear before the comment's description, and the word
``Response,'' in parentheses, will appear before our response. We have
also numbered each comment to help distinguish between different
comments. The number assigned to each comment is purely for
organizational purposes and does not signify the comment's value or
importance or the order in which it was received. Certain comments were
grouped together because the subject matter of the comments was
similar.
(Comment 1) One comment applauded the efforts put forth by the
Agency to provide industry with the opportunity for exceptions or
alternatives to FDA labeling requirements for products held by the SNS.
The comment also recognized the importance of facilitating rapid access
to large quantities of medical products in the event of an act of
terrorism or natural disaster. Another comment expressed general
agreement with the interim final rule.
(Response) We appreciate these comments in support of the rule.
Congress mandated the development of a SNS to provide for the emergency
[[Page 5697]]
health security of the United States in the event of a bioterrorist
attack or other public health emergency (section 319F-2(a) of the
Public Health Service Act (the PHS Act) (42 U.S.C. 247d-6(b))). By
providing a legal mechanism for addressing certain labeling issues
associated with medical products in the SNS without compromising their
safety, effectiveness, or availability for use in an emergency, this
rule is designed to help enable the rapid deployment of medical
countermeasures stored in the SNS in the event of such an emergency.
(Comment 2) A number of comments responded to FDA's solicitation
for comments as to whether the scope of the rule should be amended to
include medical products in other Federal, State, and local stockpiles.
One comment suggested that FDA expand the rule to include medical
products stored in hospitals. Another comment suggested that the
interim final rule should be extended to medical products stored in the
Department of Defense stockpiles. Yet another comment requested that
the scope of the rule not be extended to medical products in other
Federal, State, or local stockpiles because extending the scope of the
rule would most likely result in manufacturers seeing a high influx of
requests for exceptions or alternatives to labeling requirements under
the rule. Finally, a comment expressed general concern that the interim
final rule is flawed and therefore should not be extended to other
stockpiles.
(Response) We appreciate the comments received in response to our
solicitation. We have considered the issue, including the points raised
in these comments, and have decided not to extend the rule to other
Federal, State, and local stockpiles. With respect to the comment that
the scope of the rule should be extended to medications stored in
hospitals, we note that the SNS was created by statute to maintain
medical products under centralized control. Centralized control of the
stockpile assures that appropriate products are selected for inclusion
in the SNS and that they are then stored under appropriate conditions.
Centralized control also provides for efficient distribution in the
event of a public health emergency.
In response to the comment expressing concern that extending the
rule to include additional medical products in other Federal, State, or
local stockpiles would cause a high influx of requests for exceptions
or alternatives to the labeling requirements specified in the rule, we
recognize that extending the rule to other stockpiles may result in a
high influx of requests and further note our concern that such requests
would relate to products outside the control of SNS oversight. We
reiterate that medical products are stockpiled in the SNS under
centralized control to provide for efficient distribution in the event
of a bioterrorist attack or other public health emergency, and this
centralized control helps ensure that adequate procedures are followed
for inventory management and accounting, and for the physical security
of the stockpile. Accordingly, at this time, we decline to expand the
scope of the final rule to apply to medical products in other Federal,
State, and local stockpiles. Additionally, we note our disagreement
with the comment that the interim final rule is generally flawed. As
mandated by Congress, the SNS was created to provide for the emergency
health security of the United States in the event of a public health
emergency such as a bioterrorist attack. The interim final rule is
necessary to give FDA Center Directors the ability to grant exceptions
or alternatives to certain regulatory labeling requirements that could
adversely affect the safety, effectiveness, or availability of medical
products that are or will be included in the SNS in the event of a
public health emergency.
(Comment 3) There were two comments regarding those provisions of
the interim final rule which allow SNS officials, or any entity that
manufactures (including labeling, packing, repackaging, or relabeling),
distributes, or stores the medical products to submit a request for an
exception or alternative to the labeling requirements specified in the
rule. One comment expressed concern that the rule permitted a SNS
official to apply for alternative labeling without the consent of the
product license holder. The comment acknowledged that there may be
situations that could require a SNS official to apply for a labeling
change without the license holder's consent, such as if a license
holder went out of business, but stated that in all other cases only
the product license holder (or, in the case of an investigational
product, the anticipated biologics license application (BLA) or new
drug application (NDA) holder) should be permitted to request an
exception or alternative to the labeling requirements specified in the
rule. The comment further suggested that any request by a SNS official
for an exception or alternative to the labeling requirements specified
in the rule should be accompanied by the written concurrence of the
product license holder.
Similarly, another comment requested that the rule be amended to
allow only the product license holder or the sponsor of the
investigational new drug application (IND) to submit a request for a
labeling exception or alternative. The comment further requested that
the rule be amended to require SNS officials to first submit a request
for an alternative or exception to the labeling requirements specified
in the rule to the product license holder or IND sponsor for its
concurrence prior to submitting the request to FDA, and that the
license holder or IND sponsor be required to concur with the request
prior to SNS officials forwarding the request to FDA.
(Response) The interim final rule allows for drug, biologic, and
device application holders, or sponsors of INDs or investigational
device exemptions (IDEs), to submit requests for labeling exceptions or
alternatives. Our experience to date with respect to the interim final
rule has been that BLA holders or applicants or sponsors of INDs have
submitted all of the requests received for labeling exceptions or
alternatives with the concurrence of SNS officials. We continue to
anticipate that many, if not all, of the requests submitted under this
rule will be submitted by manufacturers with the concurrence of SNS
officials prior to or at the time a specified lot, batch, or other unit
of the product is procured by the SNS, or when an investigational
product held in the SNS has been approved, licensed, or cleared.
Nonetheless, we also continue to recognize the need for additional
flexibility regarding products stored in the SNS to ensure their
availability in the event of a public health emergency. For example, in
order to prepare for an emergency, an SNS official or FDA Center
Director could determine there is a need for labeling exceptions or
alternatives to facilitate the use of a medical countermeasure during
an emergency. We note that in this example we anticipate that the
exception or alternative required would not result in any actual change
to the product labeling, but rather would allow for the use of the
product regardless of the current labeling.
Thus, we continue to recognize that it may be necessary to allow
government officials, as well as any entity that manufactures
(including labeling, packing, repackaging, or relabeling), distributes,
or stores the medical product, to request exceptions or alternatives to
the labeling requirements specified in this rule to ensure that medical
products stored in the SNS are rapidly available for public use.
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(Comment 4) A comment suggested that FDA grant or deny a request
for an exception or alternative within 30 days from the receipt of any
request because such situations may call for rapid turnaround.
(Response) We agree that there may be situations that could call
for a rapid turnaround in responding to a request for an exception or
alternative. The intent of this rule is to ensure the rapid
availability of medical countermeasures in the event of a public health
emergency, and FDA will respond to all requests regarding the SNS as
rapidly as possible. However, we do not believe that requiring FDA to
respond within a set timeframe without accounting for the variability
and complexity of each request would necessarily serve the public
health.
(Comment 5) One comment asked what documentation would be provided
to the Department of Homeland Security's Customs and Border Protection
Agency (CBP) to allow importation of medical products that are the
subject of grants of exceptions or alternatives to labeling
requirements.
(Response) This rule has no effect on the information that must be
submitted to CBP for imported medical products. That documentation
remains unchanged. FDA and CBP will be able to make appropriate
determinations regarding products for which exceptions or alternatives
have been granted without additional information at the time of entry.
(Comment 6) A comment stated that while the rule appears to permit
only minor and technical labeling changes, it appears to be intended to
permit FDA to make additional labeling changes based on information
that becomes available to FDA after the initial label approval. The
comment argued that a change to previously approved labels based on
information not previously available alters the conditions under which
a product may be sold and may affect the product's value without
appropriate compensation to the manufacturer. Furthermore, the comment
expressed a general concern that such actions by the government may
violate the Constitution's Due Process and Takings provisions. The
comment further argued that even if such actions did not rise to the
level of Constitutional violations, they would be disincentives to
industry developing products with uses covered by the SNS. Finally, the
commenter was concerned that FDA may require a manufacturer of
investigational products to add language to the outer package labeling
of its product in the SNS after the product is licensed, approved, or
cleared.
(Response) The concerns expressed in the comment are unfounded. We
do not agree that FDA's grant of an exception or alternative to certain
FDA labeling requirements under the rule would adversely affect a
product's value. This rule applies to medical products that are or will
be held in the SNS only. The purpose of the rule is to provide for
exceptions or alternatives to certain regulatory requirements if
compliance with the requirements could adversely affect the safety,
effectiveness, or availability of these products. Therefore, we would
anticipate that this rule could encourage, as opposed to discourage,
the procurement of medical products by the SNS.
We reiterate that this rule is narrowly drafted to create necessary
exceptions or alternatives to specified labeling requirements to ensure
that medical products stored in the SNS are available for public use in
the event of an emergency. To date, we have received six requests for
exceptions or alternatives to labeling requirements, all of which have
been initiated by BLA holders or applicants or sponsors of IND
applications, with the concurrence of SNS officials. Our experience to
date is that this rule does not create disincentives to participation
in the SNS, and we note that the comment did not contain any data or
information to substantiate this concern. Furthermore, to the extent
that the comment is arguing that this rule violates the Due Process and
Takings clauses of the Constitution by affecting a product's value
without appropriate compensation to the manufacturer, as discussed
previously, we disagree. As we have explained, this rule will not
adversely affect the value of a product. We do not believe that this
rule in any way violates the Constitution.
(Comment 7) One comment expressed concern that relabeling a product
suggests product manipulation. The comment stated that over labeling or
relabeling creates the possibility for error, damage to the product and
potential confusion by the SNS and, ultimately, for the user for whom
the product is intended. Further, any of these possibilities may
increase product liability exposure for the manufacturer.
(Response) The concerns expressed in the comment are unfounded. As
stated in the preamble to the interim final rule, we recognize that
relabeling is a potentially time-consuming, costly, and labor-intensive
process that could possibly cause product mishandling, sabotage or
diversion, or could cause products to be unavailable for dispensing in
the event of an emergency. Accordingly, this rule is specifically
designed to allow FDA Center Directors to grant exceptions or
alternatives to certain labeling requirements for medical products in
the SNS to mitigate the need for relabeling. We also note that since
the development of the SNS, manufacturers, in conjunction with FDA, the
Centers for Disease Control and Prevention/SNS officials and the
Department of Health and Human Services/Biomedical Advanced Research
and Development Authority, have developed innovative labeling
mechanisms for certain products through which relabeling an
investigative product requires minimal manipulation post-licensure
(e.g., ``zipper'' labels or ``tear-off'' labels on the actual product
container).
Regarding the product liability concern, this rule does not
authorize the use of unapproved products, or of approved products for
unapproved uses in an emergency. This rule instead permits a Center
Director to authorize an exception or alternative from certain labeling
requirements. Notably, with regard to other product liability concerns
the commenter may have, the Public Readiness and Emergency Preparedness
(PREP) Act is intended to address tort liability for manufacturers in
such circumstances (42 U.S.C. 247d-6(d)).
(Comment 8) A comment stated that the rule would appear to place
burdens on a manufacturer. For example, the comment states that the
rule does not exempt a sponsor from the requirement that it include in
the company's annual report to FDA changes in labeling even when the
government initiated the change without input from the manufacturer.
The comment suggests that therefore, the company will need to track the
activities of the SNS after the product has been distributed.
(Response) FDA clarifies that under 21 CFR 201.26(e), a sponsor or
applicant would only have to report a grant of a request for an
exception or alternative of labeling requirements if the sponsor or
applicant requested the change. We also note that we expect that in the
majority of cases, this exception or alternative would be granted
during the product approval process. Accordingly, FDA does not expect
this rule to impose burdensome reporting requirements on manufacturers.
III. Legal Authority
In this final rule, FDA is amending regulations pertaining to the
content and format of medical product labeling. The provisions of this
rule allow FDA to grant exceptions or alternatives to certain of those
labeling requirements. The labeling regulations to which
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exceptions or alternatives are permitted under this rule were issued by
FDA under authority of the FD&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, and in the interim final rule, 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 FD&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 allows exceptions or alternatives for medical
products that are or will be included in the SNS.
As explained in the interim final rule, FDA has various sources of
authority to issue labeling regulations, including, for example,
sections 201(n), 502(a), and 701(a) of the FD&C Act (21 U.S.C. 321(n),
352(a), and 371(a)) for drugs (including biological products) and
devices, and sections 351(a)(1)(A) and 351(a)(2)(A) of the PHS Act (42
U.S.C. 262(a)(1)(A) and (a)(2)(A)) for biological products. In
addition, as more fully discussed in the interim final rule, 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.
IV. Analysis of Impacts
FDA has examined the impacts of the final rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all
costs and benefits of available regulatory alternatives and, when
regulation is necessary, to select regulatory approaches that maximize
net benefits (including potential economic, environmental, public
health and safety, and other advantages; distributive impacts; and
equity). The analysis of costs and benefits of available regulatory
alternatives contained in the interim final rule (72 FR 73589 at 73596)
is adopted without change in this final rule. By now reaffirming that
interim final rule, FDA has not imposed any new requirements.
Therefore, there are no additional costs and benefits associated with
this final rule.
The Regulatory Flexibility Act requires Agencies to analyze
regulatory options that would minimize any significant impact of a rule
on small entities. Because this final rule does not make any changes to
the interim final rule or our analysis included therein, the Agency
certifies that the final rule will not have a significant economic
impact on a substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires
that Agencies prepare a written statement, which includes an assessment
of anticipated costs and benefits, before issuing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $136 million, using the most current (2010) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
final rule to result in any 1-year expenditure that would meet or
exceed this amount.
V. The Paperwork Reduction Act
Sections 201.26(b), 610.68(b), 801.128(b), and 809.11(b) of this
final rule contain information collection requirements that were
submitted for review and approval to the Director of the Office of
Management and Budget (OMB), as required by section 3507(d) of the
Paperwork Reduction Act of 1995. The information collection
requirements were approved and assigned OMB control number 0910-0614
(expires August 31, 2014).
VI. 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.
VII. Federalism
In the Federal Register of October 5, 2011 (76 FR 61565), FDA
published a notification of preemption review, which was conducted in
response to a memorandum from the President that directed Federal
Agencies to review recently issued regulations to ensure that any
statements concerning preemption can be justified under legal
principles governing preemption, including those outlined in Executive
Order 13132. In this notification, FDA announced its determination that
the preamble to the interim final rule referred to statements
concerning preemption that are not justified under legal principles
governing preemption. FDA has analyzed this final rule in accordance
with the principles set forth in Executive Order 13132 and has
determined that this rule is consistent with the Executive Order.
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 adopting as
a final rule regulations permitting FDA Center Directors to grant
exceptions or alternatives to certain regulatory labeling requirements
applicable to medical products that are or will be included in the SNS.
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 FD&C Act (21 U.S.C. 379r) (nonprescription drugs) and
section 521 of the FD&C Act (21 U.S.C. 360k) (approved medical
devices). We also note that even where an express preemption provision
is not applicable, implied preemption may arise.
Accordingly, the interim final rule amending 21 CFR parts 201, 312,
314, 601, 610, 801, 807, 809, 812, and 814 which was published at 72 FR
73589 on December 28, 2007, is adopted as a final rule without change.
Dated: February 1, 2012.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2012-2558 Filed 2-3-12; 8:45 am]
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