major purpose of this rule is to expand access to investigational drugs
for patients with serious and immediately life-threatening conditions
who lack satisfactory therapeutic alternatives. Therefore, FDA
anticipates that the final rule will increase the number of patients
who obtain access to investigational drugs for treatment use. This
increase in volume will lead to more expanded access

submissions from sponsors and physicians seeking investigational drugs
for their patients and, as a consequence, will require FDA to review
more submissions. Given the relatively small burden associated with
expanded access use submissions under the previous regulations
(although such submissions are approximately one-third of all IND
submissions, the vast majority of those are for individual patients and
do not typically require substantial agency resources to review), and
the small additional burden associated with the expanded access
provisions in this final rule, FDA expects that the economic impact of
the final rule will be small.
    The final rule also attempts to minimize the potential
administrative burdens for physicians, sponsors, and FDA that will
result from an increased volume of patients obtaining investigational
drugs for expanded access use. The final rule encourages the
consolidation of multiple individual patient INDs or protocols for a
given use under an intermediate-size patient population IND or
protocol. By reducing the total volume of submissions that will have
been prepared if all patients were to obtain a drug under individual
patient INDs or protocols, consolidation will limit the additional
administrative burdens from increased patient access. In addition, by
explicitly clarifying the eligibility criteria and submission
requirements for expanded access, the final rule should make the
process of obtaining access to investigational drugs more efficient for
all affected parties.
    It is expected that any increase in the volume of submissions will
result primarily from greater numbers of patients obtaining
investigational drugs under expanded access INDs or protocols for
individual patients and intermediate-size patient populations. Because
this final rule does not significantly change the existing regulations
concerning treatment INDs or treatment protocols, the number of
patients receiving investigational drugs under these mechanisms should
be largely unaffected.
1. Individual Patient Expanded Access Submissions
    By increasing awareness of the ways individual patients can obtain
expanded access to investigational drugs for treatment use, and
decreasing the perceived difficulty of obtaining such access, the final
rule should increase the number of individual patients seeking access
to investigational drugs. FDA anticipates that this increase in
individual patient expanded access submissions will be greatest in the
years immediately following implementation of the final rule and will
at some point level off or possibly even decline. This leveling off or
decline will occur when a significant volume of individual patient
expanded access has accumulated for a variety of drugs, and the
individual patient expanded access INDs or protocols for those drugs
are then replaced with intermediate-size patient population INDs or
protocols that enroll multiple subjects. Making the transition from
multiple individual patient INDs or protocols to a single intermediate-
size patient population IND or protocol should reduce the overall
administrative burden associated with making a particular
investigational drug available for treatment use.
    From 1997 to 2005, FDA received, on average, approximately 659
individual patient and emergency IND submissions per year. Although FDA
is confident this final rule will increase this volume, it is difficult
to predict with precision the extent of the increase. There is
uncertainty concerning the extent to which patients who desire expanded
access to investigational drugs are unable to obtain them; the extent
to which better information about the mechanisms and processes for
obtaining access to investigational drugs will stimulate more patients,
or their physicians, to seek investigational drugs for expanded access
use; and the extent to which drug manufacturers will be willing to make
investigational drugs more broadly available for expanded access use.
Although FDA is confident there will be an increase in the volume of
individual patient expanded access use following issuance of this final
rule, because of these uncertainties the agency can provide only an
estimate of the range of potential increase. FDA believes that, after
publication of the final rule, it is reasonable to anticipate a 40 to
60 percent increase in the volume of individual patient expanded access
submissions by year 3. As discussed previously in this document, we
anticipate that growth will be most rapid in the years immediately
following publication of the final rule and will eventually plateau or
possibly even decline. The implications of these assumptions for the
total number of individual patient expanded access submissions are
summarized in table 3 of this document.

   Table 3.--Expected Percent Increase and Estimated No. of Individual
                   Patient Expanded Access Submissions
------------------------------------------------------------------------
       Year After            Expected Percent         Expected No. of
 Implementation of Final  Increase in Individual    Individual Patient
          Rule              Patient Submissions       Submissions\1\
------------------------------------------------------------------------
1                         20 to 40                791 to 923
------------------------------------------------------------------------
2                         30 to 50                857 to 988
------------------------------------------------------------------------
3                         40 to 60                923 to 1054
------------------------------------------------------------------------
4                         0                       923 to 1054
------------------------------------------------------------------------
5                         0                       923 to 1054
------------------------------------------------------------------------
\1\ Based on the current average of 659 individual patient treatment use
  submissions per year and the estimated percent increases in column 2.

2. Intermediate-Size Patient Population Expanded Access Submissions
    Although intermediate-size patient population expanded access has
not previously been described in the regulations, this general type of
mechanism has been used informally to make investigational drugs
available for treatment use. Based on an internal survey of review
divisions, FDA estimates that for the period 2000 through 2002 it
received approximately 55 submissions per year that would be considered
intermediate- size patient population expanded access submissions under
the final rule. The agency anticipates that this final rule will
increase the number of such submissions. Because this previously
informal mechanism will be described in the regulations for the first
time, there will be greater awareness, which is likely to stimulate
submissions. In addition, the anticipated increase in

volume of individual patient expanded access submissions discussed
previously in this document is expected to increase the number of
intermediate-size patient population expanded access submissions
because the final rule encourages the consolidation of multiple
individual patient INDs or protocols for a given expanded access use.
    The extent to which submissions for expanded access for
intermediate-size patient populations will increase is uncertain.
Section 312.315 of the final rule concerns expanded access for
intermediate-size patient populations. This section provides that FDA
may ask a sponsor to consolidate expanded access under this section
when the agency has received a significant number of requests for
individual patient expanded access to an investigational drug for the
same use. FDA does not have historical information that will permit us
to accurately predict what portion of individual patient expanded
access submissions are likely to be appropriate for consolidation.
    Based on our experience, we believe that many of the individual
patient expanded access submissions we receive will be appropriate for
consolidation. However, some individual patient expanded access
submissions will be for expanded access uses that are sufficiently rare
that it is unlikely that there will be enough similar uses to
consolidate them under an intermediate-size patient population IND or
protocol. There is also uncertainty about the extent to which sponsors
will be willing to make investigational drugs available for expanded
access use under intermediate-size patient population INDs or
protocols. Although FDA is confident that there will be growth in the
volume of intermediate-size patient population expanded access INDs or
protocols, because of the uncertainties identified, we can provide only
an estimate of the range of potential increase. FDA believes it is
reasonable to anticipate a 25 to 50 percent growth in the volume of
submissions for intermediate-size population expanded access INDs or
protocols over a 5-year period.
    Compared with the growth in individual patient expanded access
submissions, this increase is likely to be more gradual in the years
immediately following implementation of a final rule, and will increase
more sharply after 2 to 3 years as some of the increase in volume of
individual patient expanded access submissions is shifted to
intermediate-size population INDs or protocols. As in the case of
expanded access for individual patients, growth in the number of
submissions is expected to plateau or even decline after a few years.
The implications of these assumptions for the number of individual
patient expanded access submissions are summarized in table 4 of this
document.

 Table 4.--Expected Percent Increase and Estimated No. of Intermediate-
           Size Patient Population Expanded Access Submissions
------------------------------------------------------------------------
                             Expected Percent
       Year After               Increase in           Expected No. of
 Implementation of Final     Intermediate-Size       Intermediate-Size
          Rule              Patient Population      Patient Population
                                Submissions           Submissions\1\
------------------------------------------------------------------------
1                         5 to 10                 58 to 61
------------------------------------------------------------------------
2                         10 to 20                61 to 66
------------------------------------------------------------------------
3                         20 to 40                66 to 77
------------------------------------------------------------------------
4                         25 to 50                69 to 82
------------------------------------------------------------------------
5                         0                       69 to 82
------------------------------------------------------------------------
\1\ Based on the current average of 55 intermediate-size patient
  population submissions per year and the estimated percent increases in
  column 2.

3. Expanded Access under Treatment INDs and Treatment Protocols
    The number of treatment INDs and treatment protocols should be
largely unaffected by the final rule. The concept of large access
programs is well established and most drugs that meet an unmet medical
need for a serious or immediately life-threatening condition have had
some kind of large access program late in their development. Therefore,
the number of large access programs is primarily a function of the
number of new drugs to treat serious and immediately life-threatening
conditions that reach the latter stages of drug development (e.g.,
become NDA submissions). This rule is unlikely to influence that
number.
    As stated in the preamble of the proposed rule (71 FR 75147 at
75155), sponsors have instituted large expanded access programs under
treatment INDs or treatment protocols or under less formal open-label
(also referred to as open-access) protocols. The agency intends to be
more vigilant in ensuring that a use of an investigational drug that
has the characteristics of a treatment IND or treatment protocol is
submitted and authorized as such, rather than as an open-label
protocol. While this increased vigilance may increase the number of
treatment INDs or treatment protocols, any increase will be primarily
attributable to reclassifying open-label safety studies as treatment
INDs or treatment protocols rather than a net increase in the overall
number of large access programs. This reclassification should also
improve safety monitoring of large access programs without
significantly increasing administrative costs, because the costs for a
treatment IND or treatment protocol and an open-label protocol are
similar.
    Reclassification of an open-label protocol as a treatment IND or
treatment protocol may also increase publicity for, and awareness of,
the access program. Sponsors of treatment INDs or treatment protocols
may, in certain circumstances, be required to list those programs at
http://www.clinicaltrials.gov, a Web site maintained by the NIH as a
resource for patients seeking to enroll in clinical trials or obtain
access to investigational drugs for treatment use. The additional
exposure generated by this site may attract more patients than will
have had access under an open-label protocol. As a result, any given
treatment IND or treatment protocol may be somewhat more costly than a
less-publicized open-label protocol due to the volume of patients
enrolled. FDA is not able to predict the impact on patient volume as a
result of reclassifying open-label or open-access protocols as
treatment INDs or treatment protocols. However, FDA

anticipates that there will be some economies of scale, so that the
incremental costs will be relatively small on a per-patient basis. FDA
believes any added costs will be justified by the potentially greater
number of patients who will benefit from access to investigational
drugs.

E. Benefits of the Final Rule

    Because FDA currently has no data that will allow us to predict the
extent to which the amendments to existing IND regulations will
generate direct benefits for consumers, it is not possible to
accurately quantify the magnitude of any expected incremental benefits
at this time. The number of patients obtaining expanded access to
investigational drugs is expected to increase. However, because
eligible patients will have serious or immediately life-threatening
conditions that have failed to respond to available therapies, and
because the investigational drugs are unproven, FDA cannot predict the
extent to which individual patients will benefit from access to these
drugs. Thus, the following discussion describes, in general terms, the
nature of the potential benefits associated with the final rule.
    The benefits of the final rule are expected to result from improved
patient access to investigational drugs generally and from expanded
access being made available for a broader variety of disease conditions
and treatment settings. In particular, the clarification of eligibility
criteria and submission requirements will enhance patient access by
easing the administrative burdens on individual physicians seeking
investigational drugs for their patients and on sponsors who make
investigational drugs available for expanded access use. Expanded
access to investigational drugs may generate both private and social
benefits. Private benefits will accrue to individual patients receiving
drugs for expanded access use, whereas social benefits will accrue if
these private benefits are also valued by society at large, or if any
information obtained contributes to the development of new therapies
generally.
    The final rule is also designed to address concerns that many
physicians and their patients, particularly those outside of academic
medical centers, are unaware of the availability of investigational
drugs for expanded access use. In FDAMA, Congress included language in
section 561(c) of the act to authorize the Secretary to inform medical
associations, medical societies, and other appropriate persons of the
availability of investigational drugs under treatment INDs or treatment
protocols. FDA believes that this action, along with detailed
eligibility criteria and submission requirements established in the
final rule, will improve access to investigational drugs and result in
making expanded access use more widely available to patients regardless
of treatment setting.
    In formulating the final rule, FDA considered its statutory mandate
and the interests of individuals and special patient populations, drug
sponsors, and the general public. The agency found that in many
situations, individuals or special patient populations have benefited
from increased access to a drug that has not yet been approved for
marketing (e.g., in the case of cancer or HIV therapies). These
individuals or patient groups generally have serious or immediately
life-threatening conditions and have not responded to available
therapies or cannot participate in ongoing clinical trials for some
reason.
    On the other hand, unrestricted access to investigational drugs for
treatment use could reduce the patient population available for
enrollment in the clinical trials required to demonstrate safety and
efficacy in support of new drug marketing applications. If expanded
access to investigational drugs were to adversely affect the marketing
approval process, the general population will experience diminished
social benefits due to the reduced or delayed availability of new
therapies approved for marketing by FDA.
    The final rule addresses these competing interests by allowing
investigational drugs to be made available for expanded access use only
if providing the drug for the requested use will not interfere with the
initiation, conduct, or completion of clinical investigations that
could support marketing approval, or otherwise compromise the potential
development of the expanded access use. In this way, the final rule
effectively balances the interests of those patient populations who
will benefit from having greater access to investigational drugs with
the broader interests of society in having safe and effective new
therapies approved for marketing and widely available.
    The agency is also aware that allowing expanded access to
investigational drugs before they are fully evaluated for safety may
have adverse consequences for the seriously ill patients who receive
them. The safeguards in the final rule are also designed with this
concern in mind. Authorization of a particular expanded access use is
generally contingent upon a number of factors, including some evidence
of the drug's safety and effectiveness, obtaining the informed consent
of the patient, approval of an IRB, and a careful assessment of the
potential risks and benefits to the patient. In addition, the final
rule will place limits on the scope and duration of certain types of
expanded access use, require that sponsors of such INDs or protocols
monitor the expanded access use and comply with safety and annual
reporting requirements for INDs, and subject ongoing INDs or protocols
to periodic reassessment. The agency believes these safeguards will
adequately protect the safety and welfare of patients who will seek,
and may benefit from, expanded access to investigational drugs.

F. Costs of the Final Rule

    To the extent that the final rule results in an increase in the
number of expanded access submissions, drug sponsors and physicians
requesting investigational drugs on behalf of their patients will incur
some additional costs. Because the final rule does not include any new,
mandatory reporting requirements, the agency believes that the one-time
costs associated with this rule will be negligible. Thus, the
incremental burden imposed by this final rule will be in the form of
additional annual or recurring costs associated with the increased
number of expanded access submissions estimated previously in this
document.
    The agency estimates that preparation and submission of an
individual patient expanded access submission will require a total of
approximately 8 hours. This time burden will be divided among
physicians (approximately 15 percent or 1.2 hours) and nurses, nurse
practitioners, or medical administrators (approximately 85 percent or
6.8 hours). According to the U.S. Department of Labor, Bureau of Labor
Statistics,\2\ total employer costs per hour worked for employee
compensation for registered nurses in the health care and social
assistance sector was $44.21 as of March 2008. Thus, the cost of the
estimated 6.8 hours of nurse time required to prepare and submit an
individual patient expanded access submission will be approximately
$301 ($300.62 = $44.21 per hour x 6.8 hours).
---------------------------------------------------------------------------

    \2\ See http://www.bls.gov/news.release/ecec.toc.htm, last
viewed July 11, 2008. (FDA has verified the Web site address, but
FDA is not responsible for any subsequent changes to the Web site
after this document publishes in the Federal Register.)
---------------------------------------------------------------------------

    Historically, most of the treatment use requests submitted to the
agency have been prepared by physicians in the hematology/oncology
specialty category. Data available on the Internet indicate

that the median expected total compensation for a physician in the
hematology/oncology specialty category was $387,739 as of March
2008.\3\ This median total compensation figure corresponds to
approximately $186 per hour ($186.41 = $387,739 / 2,080 hours). Thus
the cost for the 1.2 hours of physician time required to prepare and
submit an individual patient expanded access submission is about $224
($223.69 = $186.41 per hour x 1.2 hours). Therefore, the agency
estimates that the total cost to prepare and submit an individual
patient expanded access submission will be about $525 ($525 = $301 +
$224). Applying this cost figure to the number of additional individual
patient expanded access submissions estimated previously in this
document suggests the pattern of incremental annual costs summarized in
table 5 of this document.
---------------------------------------------------------------------------

    \3\ See http://swz.salary.com/salarywizard/layoutscripts/swzl_
newsearch.asp, last viewed July 11, 2008. (FDA has verified the Web
site address, but FDA is not responsible for any subsequent changes
to the Web site after this document publishes in the Federal
Register).

     Table 5.--No. of Additional Individual Patient Expanded Access
                 Submissions and Estimated Annual Costs
------------------------------------------------------------------------
       Year After          Expected Increase in      Expected Cost of
 Implementation of Final   the No. of Individual   Additional Individual
          Rule            Patient Submissions\1\  Patient Submissions\2\
------------------------------------------------------------------------
1                         132-264                 $69,300 to $138,600
------------------------------------------------------------------------
2                         198-329                 $103,950 to $172,725
------------------------------------------------------------------------
3                         264-395                 $138,600 to $207,375
------------------------------------------------------------------------
4                         264-395                 $138,600 to $207,375
------------------------------------------------------------------------
5                         264-395                 $138,600 to $207,375
------------------------------------------------------------------------
\1\ Based on increases in the number of individual patient expanded
  access submissions implied by the estimates presented in table 2 of
  this document.
\2\ Based on an estimated cost of $525 per individual patient expanded
  access submission.

    Preparation and submission of an intermediate-size patient
population expanded access IND or protocol is expected to require a
total of about 120 hours of staff time. This time burden will be
divided between a Medical Director or Director of Clinical Research,
typically a medical doctor (approximately 50 percent or 60 hours), a
Regulatory Affairs Director (approximately 20 percent or 24 hours), and
a Clinical Research Associate (approximately 30 percent or 36 hours).
    Information available on the Internet suggests that the median
total compensation for a physician serving as a Medical Director is
about $316,134 per year.\4\ This translates into an estimated hourly
total compensation figure of about $152 ($151.98 = $316,134 / 2,080
hours). Thus, the cost associated with the 60 hours of Medical Director
time required to prepare and submit an intermediate-size patient
population expanded access submission is approximately $9,120 ($9,120 =
60 hours x $152).
---------------------------------------------------------------------------

    \4\ See http://swz.salary.com/salarywizard/layoutscripts/swzl_
newsearch.asp, last viewed July 11, 2008. (FDA has verified the Web
site address, but FDA is not responsible for any subsequent changes
to the Web site after this document publishes in the Federal
Register.)
---------------------------------------------------------------------------

    Information available on the Internet also indicates that the
median total compensation for a Regulatory Affairs Director is
approximately $235,149 per year.\5\ This translates into an estimated
hourly total compensation figure of about $113 ($113.05 = $235,149 /
2,080 hours). Thus, the cost associated with the 24 hours of Regulatory
Affairs Director time required to prepare and submit an intermediate-
size patient population expanded access submission is approximately
$2,712 ($2,712 = 24 hours x $113).
---------------------------------------------------------------------------

    \5\ See footnote 4 of this document.
---------------------------------------------------------------------------

    Finally, information available on the Internet indicates that the
median total compensation for a Clinical Research Associate is
approximately $86,890 per year.\6\ This translates into an estimated
hourly total compensation figure of about $42 ($41.77 = $86,890 / 2,080
hours). Thus, the cost associated with the 36 hours of Clinical
Research Associate time required to prepare and submit an intermediate-
size patient population expanded access submission is approximately
$1,512 ($1,512 = 36 hours x $42).
---------------------------------------------------------------------------

    \6\ See footnote 4 of this document.
---------------------------------------------------------------------------

    Based on the information presented, the agency estimates that the
total cost to prepare and submit an intermediate-size patient
population expanded access submission will be approximately $13,350
($13,344 = $9,120 + $2,712 + $1,512). Applying this figure to the
increases in the number of intermediate-size patient population
expanded access submissions estimated previously in this document
suggests the pattern of annual cost increases summarized in table 6 of
this document.

    Table 6.--No. of Additional Intermediate-Size Patient Population
         Expanded Access Submissions and Estimated Annual Costs
------------------------------------------------------------------------
                           Expected Increase in      Expected Cost of
       Year After               the No. of              Additional
  Implementation After       Intermediate-Size       Intermediate-Size
       Final Rule           Patient Population      Patient Population
                              Submissions\1\          Submissions\2\
------------------------------------------------------------------------
1                         3 to 6                  $40,050 to $80,100
------------------------------------------------------------------------
2                         5 to 11                 $66,750 to $146,850
------------------------------------------------------------------------
3                         11 to 22                $146,850 to $293,700
------------------------------------------------------------------------

4                         14 to 27                $186,900 to $360,450
------------------------------------------------------------------------
5                         14 to 27                $186,900 to $360,450
------------------------------------------------------------------------
\1\ Based on increases in the number of intermediate-size patient
  population expanded access submissions implied by the estimates
  presented in table 3 of this document
\2\ Based on an estimated cost of $11,000 per intermediate-size patient
  population expanded access submission.

    For reasons discussed previously in this document, the agency does
not expect that the final rule will have an impact on the overall
number of treatment INDs or treatment protocols. Therefore, FDA does
not expect the provisions of this final rule regarding treatment INDs
or treatment protocols to impose any incremental cost burden. The total
estimated variable and annual cost burdens associated with this final
rule are summarized in table 7 of this document.

                         Table 7.--Cost Summary
------------------------------------------------------------------------
     Year After
 Implementation of     One-Time      Variable Cost      Annual Cost\1\
     Final Rule       Fixed Cost
------------------------------------------------------------------------
1                    $0           $109,350 to         $109,350 to
                                   $218,700            $218,700
------------------------------------------------------------------------
2                    $0           $170,700 to         $170,700 to
                                   $319,575            $319,575
------------------------------------------------------------------------
3                    $0           $285,450 to         $285,450 to
                                   $501,075            $501,075
------------------------------------------------------------------------
4                    $0           $325,500 to         $325,500 to
                                   $567,825            $567,825
------------------------------------------------------------------------
5                    $0           $325,500 to         $325,500 to
                                   $567,825            $567,825
------------------------------------------------------------------------
\1\ Since estimated one-time fixed costs are negligible, annual costs
  equal variable costs.

    For reasons discussed previously in this document, the agency
expects that the total one-time costs of the final rule will be
negligible. FDA expects that the annual costs of this final rule will
range from a low of about $109,000 to $219,000 in the first year
following publication of the final rule, to a high of about $325,000 to
$568,000 in the fourth and fifth years. These estimates suggest total
annual costs for the final rule of between $1.2 and $2.2 million for
the 5-year period following implementation of the final rule.
    The agency expects that the estimated incremental cost burdens
associated with this final rule are likely to be widely dispersed among
affected entities for several reasons. First, given the historical
volume of various types of treatment use submissions, the agency
believes that a particular drug sponsor--or a physician acting on
behalf of a patient--will submit a request for expanded access to
investigational drugs fairly infrequently. Second, as noted previously,
the final rule encourages the consolidation of multiple expanded access
INDs or protocols for individual patients for a particular expanded
access use under an intermediate-size patient population expanded
access IND or protocol. Such consolidation should, to some extent,
offset incremental administrative burdens caused by increased patient
access. Making the transition from multiple individual patient expanded
access INDs or protocols to a single IND or protocol for an
intermediate-size patient population should reduce for sponsors the
administrative burdens associated with making a drug available for
expanded access use. In addition, provisions of the final rule are
designed to minimize the amount of information and paperwork required
to support a particular expanded access request. Physicians and drug
sponsors will need to review the rule to become familiar with its
provisions and to gather the evidence and information necessary to
support an expanded access submission. However, in instances where a
current IND already exists, a sponsor need only submit an amendment
describing the information relevant to the expanded access protocol.
Also, another sponsor or individual physician acting on behalf of a
patient may, with the written permission of the original sponsor,
reference information in the current IND already on file. The agency
believes that a majority of expanded access submissions will have such
a right of reference, either because the sponsor is also the drug
developer or the developer will generally be willing to grant the
request. To the extent that these provisions minimize the informational
burden on potential sponsors or physicians, the final rule will enhance
both efficiency and cost effectiveness.
    One comment submitted in response to the proposed rule provided an
estimate of the number of patients that might be affected by this final
rule. As part of our response, we have generated estimates of the
number additional individuals that will gain access to investigational
drugs as a result of the final rule.
    Information presented in table 5 of this document indicates that
FDA expects this final rule to generate between 132 and 395 additional
individual patient or emergency INDs per year. Thus, we estimate that
between 132 and 395 additional individuals per year will have expanded
access to investigational drugs under single patient or emergency INDs
as a result of this final rule. Information presented in table 6 of
this document indicates that FDA expects this final rule to generate
between 3 and 27 additional expanded access submissions for
intermediate-size patient populations. As discussed previously,

we believe that an intermediate-size patient population or other
expanded access program will generally include between 10 and 100
individuals. Therefore, we estimate that between 30 (30 = 3 x 10) and
2,700 (2,700 = 27 x 100) additional individuals per year will have
expanded access to investigational drugs under intermediate-size
patient populations. Finally, because FDA expects this final rule to
have no impact on the number of treatment INDs or protocols, the number
of patients with access to investigational drugs will be unaffected.
Based on this information, FDA estimates that between 162 (162 = 132 +
30) and 3,095 (3,095 = 395 + 2,700) additional individuals will receive
investigational drugs through expanded access programs as a result of
this final rule. The range of these estimates reflects significant
variation in the number of patients in intermediate-size patient
populations. These estimates are summarized in table 8 of this
document.

Table 8.--Approximate No. of Additional Individuals Affected by Expanded
                  Access Programs Under the Final Rule
------------------------------------------------------------------------
                   Expected No.                 Minimum No.  Maximum No.
                        of          No. of          of            of
     Category       Additional     Patients     Additional    Additional
                    Submissions                 Individuals  Individuals
------------------------------------------------------------------------
Individual         132 to 395    1             132           395
 Patient or
 Emergency IND
------------------------------------------------------------------------
Small Patient      3 to 27       10 to 100     30            2,700
 Population/Other
------------------------------------------------------------------------
Treatment IND or   0             100 to        0             0
 Protocol                         10,000
------------------------------------------------------------------------
Total                                          162           3,095
------------------------------------------------------------------------

G. Minimizing the Impact on Small Entities

    The agency does not believe the final rule will have a significant
economic impact on a substantial number of small entities.
Nevertheless, in the proposed rule, we recognized our uncertainty
regarding the number and size distribution of affected entities, as
well as the economic impact of the final rule on those entities, and
requested detailed comment on these important issues. We received no
comments that would cause us to change our determination that the final
rule will not have a significant economic impact on a substantial
number of small entities.
    Agency records indicate that the majority of submissions for
treatment use of investigational drugs (about 78 percent) are submitted
by commercial drug sponsors. Other entities making treatment use
submissions include government agencies (approximately 14 percent),
individual physicians (7 percent), and academic institutions (1
percent). Thus, the agency believes that the vast majority (92 percent)
of sponsors of expanded access INDs or protocols (consisting of
commercial drug sponsors or government agencies) will not be considered
small entities. The remaining 8 percent of treatment use submissions
are made by individual physicians and academic institutions that the
agency believes will meet Small Business Administration small business
criteria.
    Of the average of 659 individual patient treatment use submissions
submitted annually, very few are associated with commercial sponsors.
The vast majority are submitted by individual physicians and various
other unidentified sponsors for research purposes. Because nearly all
individual patient treatment use submissions are made by various types
of entities for research purposes, the agency believes that most of
these entities will be classified as small entities.
    Because there is currently no formal mechanism in place for
tracking the other types of expanded access (e.g., intermediate-size
patient population submissions), no data exist that will allow the
agency to identify the number of sponsors in this category that will
qualify as small entities.
    Thus, while highly uncertain, the agency believes that at least
some of the entities submitting expanded access requests will qualify
as small entities. As discussed in section VI.F of this document, the
agency expects that any incremental burden associated with the final
rule will be small and widely dispersed among affected entities.

H. Alternatives

    FDA considered several alternatives to the final rule. They are
discussed in the following paragraphs.
1. Do Not Propose Implementing Regulations for the Expanded Access
Provisions of FDAMA
    FDAMA revised the act to specifically authorize the use of
investigational new drugs by licensed physicians to diagnose, monitor,
or treat individual patients who have a serious disease or condition
if, among other things, the physician determines that the person has no
comparable or satisfactory alternative therapy to diagnose, monitor, or
treat the disease or condition, and that the probable risk from the
investigational drug is not greater than the probable risk from the
disease or condition; and FDA determines that there is sufficient
evidence of safety and effectiveness to support the use of the
investigational drug. FDAMA also largely incorporated into the act
FDA's current regulation concerning treatment INDs or treatment
protocols under which large populations currently receive
investigational drugs for treatment use. Because FDAMA did not require
that FDA adopt implementing regulations, the agency could have chosen
not to do so.
    However, the agency believes that implementing regulations will
further improve expanded access to investigational drugs for treatment
use. One of the major criticisms about access to investigational drugs
is that the criteria for authorizing access are unclear and that there
is not broad knowledge among affected, or potentially affected, parties
about the mechanisms or procedures to obtain access. FDA believes the
final regulations are needed to address these concerns. The regulations
provide to sponsors, patients, and licensed physicians who will be
seeking investigational drugs for their patients clear direction about
the criteria for authorizing expanded access and what information must
be submitted to the agency to enable it to evaluate a proposed expanded
access submission. Clearer direction and greater knowledge of the
mechanisms and procedures for obtaining investigational drugs for
expanded access use should reduce barriers to access.

2. Propose a Regulation Describing Only Individual Patient Expanded
Access and the Treatment IND or Treatment Protocol
    As discussed in the previous paragraphs, FDAMA specifically
authorized the use of investigational new drugs by licensed physicians
to diagnose, monitor, or treat individual patients in certain
circumstances. FDAMA also essentially repeated FDA's current regulation
concerning treatment INDs or treatment protocols under which large
populations currently receive investigational drugs for treatment use.
    FDA could have chosen to adopt regulations that described only
these two categories of expanded access. However, FDA has had a long
history of using an informal mechanism to make investigational drugs
available to intermediate-size patient populations. This mechanism has
been used in situations in which both: (1) The expanded access use did
not meet the criteria for a treatment IND under the previous regulation
and (2) it would have been excessively burdensome for sponsors and FDA
to require large numbers of individual patient INDs for the same use.
The agency concluded that, consistent with the terminology of section
561(b)(4) of the act, it is preferable to establish an intermediate
category for expanded access, with additional criteria and monitoring
requirements, that will be used for more than an individual patient,
but fewer than the large numbers of patients in treatment INDs or
treatment protocols.
    In FDA's experience, there is often a need for a middle ground
between an individual patient IND or protocol and a treatment IND or
treatment protocol. For some drugs in development, there is
considerable demand for expanded access before the use meets the
criteria for a treatment IND or treatment protocol. There are also
situations in which investigational drugs that are not being actively
developed are the best available therapy for a significant number of
patients and should be made available to patients under an expanded
access process. In these situations, making the drug available under a
series of individual patient expanded access INDs or protocols is
burdensome on physicians, sponsors, and FDA, and makes it difficult to
monitor the expanded access use to identify significant safety concerns
such as serious adverse events.
    Describing this intermediate category in the regulations is also
consistent with FDA's goal of maximizing awareness of expanded access
programs by being more transparent about the processes for making drugs
available for expanded access. As stated previously, FDA has used this
intermediate category informally in the past and believes it will have
reason to use this category in the future. Therefore, FDA believes it
is appropriate to formalize and fully describe in the regulations the
intermediate expanded access category, as well as the two other
categories of expanded access.
3. Propose a Regulation Describing More Than Three Expanded Access
Categories
    FDA also considered proposing a rule that will include more than
three expanded access categories, but rejected this alternative. In
internal discussions, FDA found that the distinctions between the
proposed categories and the additional categories it considered were
unclear. FDA was concerned that the additional categories would create
confusion rather than provide the clarity that is the goal of the final
regulations. FDA concluded that the additional categories could be
merged into the three proposed categories and that these categories
will be able to provide access to investigational drugs in all
situations FDA is likely to encounter.

VII. Paperwork Reduction Act of 1995

    This final rule contains information collection requirements that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520) (the
PRA). The title, description, and respondent description of the
information collection provisions are shown below with an estimate of
the annual reporting burden. Our estimate includes the time for
reviewing instructions, searching existing data sources, gathering and
maintaining the data needed, and completing and reviewing each
collection of information.
    Title: Expanded Access to Investigational Drugs for Treatment Use
    Description: The final rule clarifies existing regulations and
revises them by adding new types of expanded access for treatment use.
Under the final rule, expanded access to investigational drugs will be
available to individual patients, including in emergencies; to
intermediate-size patient populations; and to larger populations under
a treatment protocol or IND. The final rule is intended to improve
access to investigational drugs for patients with serious or
immediately life-threatening diseases or conditions who lack other
therapeutic options and may benefit from such therapies.

A. The Final Rule

1. Submission Requirements for All Expanded Access Uses
    Section 312.305(b) describes the submission requirements applicable
to all types of expanded access.
    Section 312.305(b)(1) states that an expanded access submission is
required for each type of expanded access. The submission may be a new
IND or a protocol amendment to an existing IND. Information required
for a submission may be supplied by referring to pertinent information
contained in an existing IND if the sponsor of the existing IND grants
a right of reference to the IND.
    Section 312.305(b)(2) describes the expanded access submission
requirements. The following items must be included:
     A cover sheet (Form FDA 1571) meeting the requirements of
Sec.  312.23(a);
     The rationale for the intended use of the drug, including
a list of available therapeutic options that will ordinarily be tried
before resorting to the investigational drug or an explanation of why
the use of the investigational drug is preferable to the use of
available therapeutic options;
     The criteria for patient selection; or, for an individual
patient, a description of the patient's disease or condition, including
recent medical history and previous treatments used for the disease or
condition;
     The method of administration of the drug, dose, and
duration of therapy;
     A description of the facility where the drug will be
manufactured;
     Chemistry, manufacturing, and controls information
adequate to ensure the proper identification, quality, purity, and
strength of the investigational drug;
     Pharmacology and toxicology information adequate to
conclude that the drug is reasonably safe at the dose and duration for
expanded access use (ordinarily, information that will be adequate to
permit clinical testing of the drug in a population of the size
expected to be treated); and
     A description of clinical procedures, laboratory tests, or
other monitoring necessary to evaluate the effects of the drug and
minimize its risks.
2. Individual Patient Expanded Access
    Section 312.310(b) contains additional submission requirements that
apply to use of an investigational drug for the treatment of an
individual patient by a licensed physician. The expanded access
submission must include information adequate to satisfy

FDA that the criteria for all expanded access uses and those specific
to individual patient expanded access have been met. The individual
patient expanded access criteria are:
     The physician must determine that the probable risk to the
person from the investigational drug is not greater than the probable
risk from the disease or condition, and
     FDA must determine that the patient cannot obtain the drug
under another type of IND.
    Section 312.310(b)(1) states that if the drug is the subject of an
existing IND, the expanded access submission may be made by a
commercial sponsor or by a licensed physician.
    Section 312.310(b)(2) states that a sponsor may satisfy the
submission requirements by amending its existing IND to include an
individual patient expanded access protocol.
    Section 312.310(b)(3) states that a licensed physician may satisfy
the submission requirements by obtaining a right of reference to
pertinent information in the IND and providing any other required
information not contained in the IND (usually only the information
specific to the individual patient).
3. Intermediate-Size Patient Populations
    Section 312.315(c) states that an expanded access submission for an
intermediate-size patient population must include information adequate
to satisfy FDA that the criteria for all expanded access uses and those
specific to intermediate-size patient populations have been met. The
intermediate-size patient population criteria are: (1) There is enough
evidence that the drug is safe at the dose and duration proposed for
treatment use to justify a clinical trial of the drug in the
approximate number of patients expected to receive the drug for
treatment use; and (2) there is at least preliminary clinical evidence
of effectiveness of the drug or of a plausible pharmacologic effect of
the drug to make expanded access use a reasonable therapeutic option in
the anticipated patient population. Section 312.315(c) contains
additional submission requirements that apply to use of an
investigational drug for intermediate-size patient populations. The
expanded access submission must state whether the drug is being
developed or is not being developed and describe the patient population
to be treated. If the drug is not being actively developed, the sponsor
must explain why the drug cannot currently be developed for the
expanded access use and under what circumstances the drug could be
developed. If the drug is being studied in a clinical trial, the
sponsor must explain why the patients to be treated cannot be enrolled
in the clinical trial and under what circumstances the sponsor will
conduct a clinical trial in these patients.
4. Treatment IND or Protocol
    Section 312.320 describes the treatment IND or treatment protocol
currently codified in Sec. Sec.  312.34 and 312.35. Section 312.320(b)
states that the expanded access submission must include information
adequate to satisfy FDA that the criteria for all expanded access uses
and those specific to the treatment IND or protocol have been met. The
criteria specific to a treatment IND or treatment protocol are: (1) The
drug is being investigated in a controlled clinical trial designed to
support a marketing application for the expanded access use or all
clinical trials of the drug have been completed, (2) the sponsor is
pursuing marketing approval of the drug for the expanded access use
with due diligence, and (3) there is sufficient clinical evidence of
safety and effectiveness to support the treatment use. Such evidence
will ordinarily consist of data from phase 3 trials, but could consist
of compelling data from completed phase 2 trials. When the expanded
access use is for an immediately life-threatening disease or condition,
the available scientific evidence, taken as a whole, could provide a
reasonable basis to conclude that the investigational drug may be
effective for the expanded access use and will not expose patients to
an unreasonable and significant risk of illness or injury. This
evidence will ordinarily consist of clinical data from phase 3 or phase
2 trials, but could be based on more preliminary clinical evidence.

B. Estimates of Reporting Burden

    Our estimate of the amount of time required to complete an expanded
access submission is based on the assumption that either the submission
will be made by the drug developer or the submitter will have obtained
a right of reference from the drug developer. We expect an increase in
the number of submissions for expanded access for individual patients
and for intermediate-size patient populations as a result of this final
rule.
1. Individual Patient Expanded Access
    From 1997 to 2005, we received on average approximately 659
submissions for the treatment use of investigational drugs by
individual patients per year. This estimate is based on our records of
the number of individual patient IND submissions (primarily from
physicians) and a survey of our review divisions on the prevalence of
individual patient protocol exception submissions received from
commercial drug sponsors. As indicated in the table below, we expect an
increase in the number of individual patient expanded access
submissions because the final rule will increase awareness of the
option for individual patients to gain access to investigational drugs
and decrease the perceived difficulty of obtaining such access. We
anticipate that the increase in individual patient expanded access INDs
or protocols will be greatest in the years immediately following
implementation of the final rule and will at some point level off or
possibly even decline. This leveling off or decline will occur when a
significant volume of individual patient expanded access INDs or
protocols have accumulated for a variety of drugs, and the individual
patient expanded access INDs or protocols for those drugs are then
replaced with intermediate-size patient population expanded access INDs
or protocols that enroll multiple subjects.
    We estimate that preparation and submission of an individual
patient expanded access IND or protocol submission will require a total
of approximately 8 hours.
2. Intermediate-Size Patient Population Expanded Access
    Although intermediate-size patient population expanded access INDs
or protocols have not previously been described in regulation,
investigational drugs have been made available informally for treatment
use to such populations. Based on an internal survey of our review
divisions, we estimate that, for the period 2000 through 2002, we
received approximately 55 submissions per year that we consider
expanded access for an intermediate-size patient population under the
final rule. As indicated in table 9, we anticipate that this number
will increase under the final rule because there will be greater
awareness of this option. In addition, the anticipated increase in
volume of submissions for expanded access for individual patients
discussed previously is expected to increase the number of submissions
for expanded access for intermediate-size patient populations because
the final rule encourages the consolidation of multiple individual
patient INDs or protocols for a given expanded access use.
    Information provided by our review divisions indicates that
preparation and

submission of an intermediate-size patient population IND will require
a total of approximately 120 hours.
3. Treatment IND or Treatment Protocol
    We do not expect the final rule to have an impact on the overall
number of treatment INDs or treatment protocols because this type of
expanded access is already established in FDA regulations at Sec. Sec.
312.34 and 312.35. Therefore, we do not expect the provisions of this
final rule regarding treatment INDs or treatment protocols to impose
any increased paperwork burden. The burden for these submissions, as
currently required under Sec.  312.35, is already approved by OMB under
OMB control number 0910-0014.
    Description of Respondents: Licensed physicians and manufacturers,
including small business manufacturers.
    Table 9 of this document presents the annualized reporting burden
for the total number of expanded access submissions by type of expanded
access use. The estimates in the table are based on data from section
VI of this document and are calculated by averaging the projected
number of submissions for the first 3 years after implementation of
this final rule.

                                 Table 9.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                      No. of         No. of Responses                           Hours per
21 CFR Section     Respondents        per Respondent      Total  Responses       Response         Total Hours
----------------------------------------------------------------------------------------------------------------
Sec.  Sec.                    988                     1                988                  8              7,904
 312.305 and
 312.310(b)
----------------------------------------------------------------------------------------------------------------
Sec.  Sec.                     68                     1                 68                120              8,160
 312.305(b)
 and
 312.315(c)
----------------------------------------------------------------------------------------------------------------
Total                                                                                16,064
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection.

    The information collection provisions in this final rule have been
submitted to OMB for review. Prior to the effective date of this final
rule, FDA will publish a notice in the Federal Register announcing
OMB's decision to approve, modify, or disapprove the information
collection provisions in this final rule. 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. Federalism

    FDA has analyzed this final rule in accordance with the principles
set forth in Executive Order 13132. FDA has tentatively determined that
the rule does not contain policies that have substantial direct effects
on the States, on the relationship between the National Government and
the States, or on the distribution of power and responsibilities among
the various levels of government. Accordingly, the agency has
tentatively concluded that the rule does not contain policies that have
federalism implications as defined in the order and, consequently, a
federalism summary impact statement is not required.

List of Subjects

21 CFR Part 312

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

21 CFR Part 316

    Administrative practice and procedure, Drugs, Investigations,
Medical research, Reporting and recordkeeping requirements.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR parts
312 and 316 are amended as follows:

PART 312--INVESTIGATIONAL NEW DRUG APPLICATION

0
1. The authority citation for 21 CFR part 312 is revised to read as
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 355, 360bbb, 371;
42 U.S.C. 262.

0
2. Section 312.30 is amended by revising paragraph (c) to read as
follows:

Sec.  312.30  Protocol amendments.

* * * * *
     (c) New investigator. A sponsor shall submit a protocol amendment
when a new investigator is added to carry out a previously submitted
protocol, except that a protocol amendment is not required when a
licensed practitioner is added in the case of a treatment protocol
under Sec.  312.315 or Sec.  312.320. Once the investigator is added to
the study, the investigational drug may be shipped to the investigator
and the investigator may begin participating in the study. The sponsor
shall notify FDA of the new investigator within 30 days of the
investigator being added.
* * * * *

Sec.  312.34   [Removed]

0
3. Section 312.34 is removed.

Sec.  312.35   [Removed]

0
4. Section 312.35 is removed.

Sec.  312.36   [Removed]

0
5. Section 312.36 is removed.

0
6. Section 312.42 is amended by revising paragraph (b)(3) to read as
follows:

Sec.  312.42   Clinical holds and requests for modification.

* * * * *
    (b) * * *
    (3) Clinical hold of an expanded access IND or expanded access
protocol. FDA may place an expanded access IND or expanded access
protocol on clinical hold under the following conditions:
    (i) Final use. FDA may place a proposed expanded access IND or
treatment use protocol on clinical hold if it is determined that:
    (A) The pertinent criteria in subpart I of this part for permitting
the expanded access use to begin are not satisfied; or
    (B) The expanded access IND or expanded access protocol does not
comply with the requirements for expanded access submissions in subpart
I of this part.
    (ii) Ongoing use. FDA may place an ongoing expanded access IND or
expanded access protocol on clinical hold if it is determined that the
pertinent criteria in subpart I of this part for permitting the
expanded access are no longer satisfied.
* * * * *

0
7. Part 312 is amended by adding and reserving subpart H, and by adding
subpart I, consisting of Sec. Sec.  312.300 through 312.320, to read as
follows:
Subpart H--[Reserved]
Subpart I--Expanded Access to Investigational Drugs for Treatment Use
Sec.
312.300 General.

312.305 Requirements for all expanded access uses.
312.310 Individual patients, including for emergency use.
312.315 Intermediate-size patient populations.
312.320 Treatment IND or treatment protocol.

Subpart I--Expanded Access to Investigational Drugs for Treatment
Use

Sec.  312.300  General.

    (a) Scope. This subpart contains the requirements for the use of
investigational new drugs and approved drugs where availability is
limited by a risk evaluation and mitigation strategy (REMS) when the
primary purpose is to diagnose, monitor, or treat a patient's disease
or condition. The aim of this subpart is to facilitate the availability
of such drugs to patients with serious diseases or conditions when
there is no comparable or satisfactory alternative therapy to diagnose,
monitor, or treat the patient's disease or condition.
    (b) Definitions. The following definitions of terms apply to this
subpart:
    Immediately life-threatening disease or condition means a stage of
disease in which there is reasonable likelihood that death will occur
within a matter of months or in which premature death is likely without
early treatment.
    Serious disease or condition means a disease or condition
associated with morbidity that has substantial impact on day-to-day
functioning. Short-lived and self-limiting morbidity will usually not
be sufficient, but the morbidity need not be irreversible, provided it
is persistent or recurrent. Whether a disease or condition is serious
is a matter of clinical judgment, based on its impact on such factors
as survival, day-to-day functioning, or the likelihood that the
disease, if left untreated, will progress from a less severe condition
to a more serious one.

Sec.  312.305   Requirements for all expanded access uses.

    The criteria, submission requirements, safeguards, and beginning
treatment information set out in this section apply to all expanded
access uses described in this subpart. Additional criteria, submission
requirements, and safeguards that apply to specific types of expanded
access are described in Sec. Sec.  312.310 through 312.320.
    (a) Criteria. FDA must determine that:
    (1) The patient or patients to be treated have a serious or
immediately life-threatening disease or condition, and there is no
comparable or satisfactory alternative therapy to diagnose, monitor, or
treat the disease or condition;
    (2) The potential patient benefit justifies the potential risks of
the treatment use and those potential risks are not unreasonable in the
context of the disease or condition to be treated; and
    (3) Providing the investigational drug for the requested use will
not interfere with the initiation, conduct, or completion of clinical
investigations that could support marketing approval of the expanded
access use or otherwise compromise the potential development of the
expanded access use.
    (b) Submission. (1) An expanded access submission is required for
each type of expanded access described in this subpart. The submission
may be a new IND or a protocol amendment to an existing IND.
Information required for a submission may be supplied by referring to
pertinent information contained in an existing IND if the sponsor of
the existing IND grants a right of reference to the IND.
    (2) The expanded access submission must include:
    (i) A cover sheet (Form FDA 1571) meeting the requirements of Sec.
312.23(a);
    (ii) The rationale for the intended use of the drug, including a
list of available therapeutic options that would ordinarily be tried
before resorting to the investigational drug or an explanation of why
the use of the investigational drug is preferable to the use of
available therapeutic options;
    (iii) The criteria for patient selection or, for an individual
patient, a description of the patient's disease or condition, including
recent medical history and previous treatments of the disease or
condition;
    (iv) The method of administration of the drug, dose, and duration
of therapy;
    (v) A description of the facility where the drug will be
manufactured;
    (vi) Chemistry, manufacturing, and controls information adequate to
ensure the proper identification, quality, purity, and strength of the
investigational drug;
    (vii) Pharmacology and toxicology information adequate to conclude
that the drug is reasonably safe at the dose and duration proposed for
expanded access use (ordinarily, information that would be adequate to
permit clinical testing of the drug in a population of the size
expected to be treated); and
    (viii) A description of clinical procedures, laboratory tests, or
other monitoring necessary to evaluate the effects of the drug and
minimize its risks.
    (3) The expanded access submission and its mailing cover must be
plainly marked ``EXPANDED ACCESS SUBMISSION.'' If the expanded access
submission is for a treatment IND or treatment protocol, the applicable
box on Form FDA 1571 must be checked.
    (c) Safeguards. The responsibilities of sponsors and investigators
set forth in subpart D of this part are applicable to expanded access
use under this subpart as described in this paragraph.
    (1) A licensed physician under whose immediate direction an
investigational drug is administered or dispensed for an expanded
access use under this subpart is considered an investigator, for
purposes of this part, and must comply with the responsibilities for
investigators set forth in subpart D of this part to the extent they
are applicable to the expanded access use.
    (2) An individual or entity that submits an expanded access IND or
protocol under this subpart is considered a sponsor, for purposes of
this part, and must comply with the responsibilities for sponsors set
forth in subpart D of this part to the extent they are applicable to
the expanded access use.
    (3) A licensed physician under whose immediate direction an
investigational drug is administered or dispensed, and who submits an
IND for expanded access use under this subpart is considered a sponsor-
investigator, for purposes of this part, and must comply with the
responsibilities for sponsors and investigators set forth in subpart D
of this part to the extent they are applicable to the expanded access
use.
    (4) Investigators. In all cases of expanded access, investigators
are responsible for reporting adverse drug events to the sponsor,
ensuring that the informed consent requirements of part 50 of this
chapter are met, ensuring that IRB review of the expanded access use is
obtained in a manner consistent with the requirements of part 56 of
this chapter, and maintaining accurate case histories and drug
disposition records and retaining records in a manner consistent with
the requirements of Sec.  312.62. Depending on the type of expanded
access, other investigator responsibilities under subpart D may also
apply.
    (5) Sponsors. In all cases of expanded access, sponsors are
responsible for submitting IND safety reports and annual reports (when
the IND or protocol continues for 1 year or longer) to FDA as required
by Sec. Sec.  312.32 and 312.33, ensuring that licensed physicians are
qualified to administer the investigational drug for the expanded
access use, providing licensed

physicians with the information needed to minimize the risk and
maximize the potential benefits of the investigational drug (the
investigator's brochure must be provided if one exists for the drug),
maintaining an effective IND for the expanded access use, and
maintaining adequate drug disposition records and retaining records in
a manner consistent with the requirements of Sec.  312.57. Depending on
the type of expanded access, other sponsor responsibilities under
subpart D may also apply.
    (d) Beginning treatment--(1) INDs. An expanded access IND goes into
effect 30 days after FDA receives the IND or on earlier notification by
FDA that the expanded access use may begin.
    (2) Protocols. With the following exceptions, expanded access use
under a protocol submitted under an existing IND may begin as described
in Sec.  312.30(a).
    (i) Expanded access use under the emergency procedures described in
Sec.  312.310(d) may begin when the use is authorized by the FDA
reviewing official.
    (ii) Expanded access use under Sec.  312.320 may begin 30 days
after FDA receives the protocol or upon earlier notification by FDA
that use may begin.
    (3) Clinical holds. FDA may place any expanded access IND or
protocol on clinical hold as described in Sec.  312.42.

Sec.  312.310   Individual patients, including for emergency use.

    Under this section, FDA may permit an investigational drug to be
used for the treatment of an individual patient by a licensed
physician.
    (a) Criteria. The criteria in Sec.  312.305(a) must be met; and the
following determinations must be made:
    (1) The physician must determine that the probable risk to the
person from the investigational drug is not greater than the probable
risk from the disease or condition; and
    (2) FDA must determine that the patient cannot obtain the drug
under another IND or protocol.
    (b) Submission. The expanded access submission must include
information adequate to demonstrate that the criteria in Sec.
312.305(a) and paragraph (a) of this section have been met. The
expanded access submission must meet the requirements of Sec.
312.305(b).
    (1) If the drug is the subject of an existing IND, the expanded
access submission may be made by the sponsor or by a licensed
physician.
    (2) A sponsor may satisfy the submission requirements by amending
its existing IND to include a protocol for individual patient expanded
access.
    (3) A licensed physician may satisfy the submission requirements by
obtaining from the sponsor permission for FDA to refer to any
information in the IND that would be needed to support the expanded
access request (right of reference) and by providing any other required
information not contained in the IND (usually only the information
specific to the individual patient).
    (c) Safeguards. (1) Treatment is generally limited to a single
course of therapy for a specified duration unless FDA expressly
authorizes multiple courses or chronic therapy.
    (2) At the conclusion of treatment, the licensed physician or
sponsor must provide FDA with a written summary of the results of the
expanded access use, including adverse effects.
    (3) FDA may require sponsors to monitor an individual patient
expanded access use if the use is for an extended duration.
    (4) When a significant number of similar individual patient
expanded access requests have been submitted, FDA may ask the sponsor
to submit an IND or protocol for the use under Sec.  312.315 or Sec.
312.320.
    (d) Emergency procedures. If there is an emergency that requires
the patient to be treated before a written submission can be made, FDA
may authorize the expanded access use to begin without a written
submission. The FDA reviewing official may authorize the emergency use
by telephone.
    (1) Emergency expanded access use may be requested by telephone,
facsimile, or other means of electronic communications. For
investigational biological drug products regulated by the Center for
Biologics Evaluation and Research, the request should be directed to
the Office of Communication, Outreach and Development, Center for
Biologics Evaluation and Research,<PHONE_NUMBER> or 1-800-835-4709, e-
mail<EMAIL_ADDRESS>For all other investigational drugs, the
request for authorization should be directed to the Division of Drug
Information, Center for Drug Evaluation and Research,<PHONE_NUMBER>, e-
mail<EMAIL_ADDRESS>After normal working hours, the request
should be directed to the FDA Office of Emergency Operations, 301-443-
1240, e-mail<EMAIL_ADDRESS>    (2) The licensed physician or sponsor must explain how the expanded
access use will meet the requirements of Sec. Sec.  312.305 and 312.310
and must agree to submit an expanded access submission within 15
working days of FDA's authorization of the use.

Sec.  312.315   Intermediate-size patient populations.

    Under this section, FDA may permit an investigational drug to be
used for the treatment of a patient population smaller than that
typical of a treatment IND or treatment protocol. FDA may ask a sponsor
to consolidate expanded access under this section when the agency has
received a significant number of requests for individual patient
expanded access to an investigational drug for the same use.
    (a) Need for expanded access. Expanded access under this section
may be needed in the following situations:
    (1) Drug not being developed. The drug is not being developed, for
example, because the disease or condition is so rare that the sponsor
is unable to recruit patients for a clinical trial.
    (2) Drug being developed. The drug is being studied in a clinical
trial, but patients requesting the drug for expanded access use are
unable to participate in the trial. For example, patients may not be
able to participate in the trial because they have a different disease
or stage of disease than the one being studied or otherwise do not meet
the enrollment criteria, because enrollment in the trial is closed, or
because the trial site is not geographically accessible.
    (3) Approved or related drug. (i) The drug is an approved drug
product that is no longer marketed for safety reasons or is unavailable
through marketing due to failure to meet the conditions of the approved
application, or
    (ii) The drug contains the same active moiety as an approved drug
product that is unavailable through marketing due to failure to meet
the conditions of the approved application or a drug shortage.
    (b) Criteria. The criteria in Sec.  312.305(a) must be met; and FDA
must determine that:
    (1) There is enough evidence that the drug is safe at the dose and
duration proposed for expanded access use to justify a clinical trial
of the drug in the approximate number of patients expected to receive
the drug under expanded access; and
    (2) There is at least preliminary clinical evidence of
effectiveness of the drug, or of a plausible pharmacologic effect of
the drug to make expanded access use a reasonable therapeutic option in
the anticipated patient population.
    (c) Submission. The expanded access submission must include
information adequate to satisfy FDA that the criteria in Sec.
312.305(a) and paragraph (b) of this section have been met. The
expanded

access submission must meet the requirements of Sec.  312.305(b). In
addition:
    (1) The expanded access submission must state whether the drug is
being developed or is not being developed and describe the patient
population to be treated.
    (2) If the drug is not being actively developed, the sponsor must
explain why the drug cannot currently be developed for the expanded
access use and under what circumstances the drug could be developed.
    (3) If the drug is being studied in a clinical trial, the sponsor
must explain why the patients to be treated cannot be enrolled in the
clinical trial and under what circumstances the sponsor would conduct a
clinical trial in these patients.
    (d) Safeguards. (1) Upon review of the IND annual report, FDA will
determine whether it is appropriate for the expanded access to continue
under this section.
    (i) If the drug is not being actively developed or if the expanded
access use is not being developed (but another use is being developed),
FDA will consider whether it is possible to conduct a clinical study of
the expanded access use.
    (ii) If the drug is being actively developed, FDA will consider
whether providing the investigational drug for expanded access use is
interfering with the clinical development of the drug.
    (iii) As the number of patients enrolled increases, FDA may ask the
sponsor to submit an IND or protocol for the use under Sec.  312.320.
    (2) The sponsor is responsible for monitoring the expanded access
protocol to ensure that licensed physicians comply with the protocol
and the regulations applicable to investigators.

Sec.  312.320  Treatment IND or treatment protocol.

    Under this section, FDA may permit an investigational drug to be
used for widespread treatment use.
    (a) Criteria. The criteria in Sec.  312.305(a) must be met, and FDA
must determine that:
    (1) Trial status. (i) The drug is being investigated in a
controlled clinical trial under an IND designed to support a marketing
application for the expanded access use, or
    (ii) All clinical trials of the drug have been completed; and
    (2) Marketing status. The sponsor is actively pursuing marketing
approval of the drug for the expanded access use with due diligence;
and
    (3) Evidence. (i) When the expanded access use is for a serious
disease or condition, there is sufficient clinical evidence of safety
and effectiveness to support the expanded access use. Such evidence
would ordinarily consist of data from phase 3 trials, but could consist
of compelling data from completed phase 2 trials; or
    (ii) When the expanded access use is for an immediately life-
threatening disease or condition, the available scientific evidence,
taken as a whole, provides a reasonable basis to conclude that the
investigational drug may be effective for the expanded access use and
would not expose patients to an unreasonable and significant risk of
illness or injury. This evidence would ordinarily consist of clinical
data from phase 3 or phase 2 trials, but could be based on more
preliminary clinical evidence.
    (b) Submission. The expanded access submission must include
information adequate to satisfy FDA that the criteria in Sec.
312.305(a) and paragraph (a) of this section have been met. The
expanded access submission must meet the requirements of Sec.
312.305(b).
    (c) Safeguard. The sponsor is responsible for monitoring the
treatment protocol to ensure that licensed physicians comply with the
protocol and the regulations applicable to investigators.

PART 316--ORPHAN DRUGS

0
8. The authority citation for 21 CFR part 316 continues to read as
follows:

    Authority:  21 U.S.C. 360aa, 360bb, 360cc, 360dd, 371.

0
9. Section 316.40 is revised to read as follows:

Sec.  316.40   Treatment use of a designated orphan drug.

    Prospective investigators seeking to obtain treatment use of
designated orphan drugs may do so as provided in subpart I of this
chapter.

    Dated: July 20, 2009.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E9-19005 Filed 8-12-09; 8:45 am]

BILLING CODE 4160-01-S


[Federal Register Volume 78, Number 133 (Thursday, July 11, 2013)]
[Notices]
[Pages 41792-41793]
[FR Doc No: 2013-16625]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

Combined Notice of Filings 1

    Take notice that the Commission received the following electric
rate filings:

    Docket Numbers: ER10-1484-008.
    Applicants: Shell Energy North America (US), L.P.
    Description: Updated Market Power Analysis for the Southwest Region
of Shell Energy North America (US), L.P.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5384.
    Comments Due: 5 p.m. ET 8/30/13.

    Docket Numbers: ER10-1674-003.
    Applicants: Deseret Generation & Transmission Co-operative.
    Description: Updated Market Power Analysis to be effective 7/1/
2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5306.
    Comments Due: 5 p.m. ET 8/30/13.

    Docket Numbers: ER10-2474-004; ER10-2475-004.
    Applicants: Sierra Pacific Power Company, Nevada Power Company.
    Description: Updated Market Power Analysis for the Northwest Region
of Sierra Pacific Power Company, et al.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5387.
    Comments Due: 5 p.m. ET 8/30/13.

    Docket Numbers: ER10-3077-003; ER10-3075-003; ER10-3076-003; ER10-
3074-003; ER10-3071-003; ER10-3257-002.
    Applicants: CalPeak Power LLC, CalPeak Power--Border LLC, CalPeak
Power--Enterprise LLC, CalPeak Power--Vaca Dixon LLC, CalPeak Power--
Panoche LLC, Starwood Power-Midway, LLC.
    Description: Updated Market Power Analysis for the Southwest Region
of the CalPeak Entities, et al.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5389.
    Comments Due: 5 p.m. ET 8/30/13.

    Docket Numbers: ER13-1661-001.
    Applicants: NEXTENERGY SERVICES LLC.
    Description: Amended Tariff and Asset Appendix to be effective 8/
10/2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5319.
    Comments Due: 5 p.m. ET 7/22/13.

    Docket Numbers: ER13-1878-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Original Service Agreement No. 3587--Queue Position
Y3-049 to be effective 5/30/2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5252.
    Comments Due: 5 p.m. ET 7/22/13.

    Docket Numbers: ER13-1879-000.
    Applicants: PJM Interconnection, L.L.C.
    Description: Original Service Agreement No. 3586--Queue Position
Y3-048 to be effective 5/30/2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5262.
    Comments Due: 5 p.m. ET 7/22/13.

    Docket Numbers: ER13-1880-000.
    Applicants: New England Power Pool Participants Committee, ISO New
England Inc.
    Description: Revisions to Forward Capacity Auction Market Clearing
Function to be effective 9/2/2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5264.
    Comments Due: 5 p.m. ET 7/22/13

    Docket Numbers: ER13-1881-000.
    Applicants: Cabazon Wind Partners, LLC.
    Description: SW Triennial & Tariff Revisions to be effective 7/2/
2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5265.
    Comments Due: 5 p.m. ET 8/30/13.

    Docket Numbers: ER13-1882-000.
    Applicants: Whitewater Hill Wind Partners, LLC.
    Description: SW Triennial & Tariff Revisions to be effective 7/2/
2013.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5290.
    Comments Due: 5 p.m. ET 8/30/13.

    Take notice that the Commission received the following electric
securities filings:

    Docket Numbers: ES13-34-000.
    Applicants: ISO New England Inc.
    Description: Application of ISO New England Inc. under Section 204
of the Federal Power Act.
    Filed Date: 7/1/13.
    Accession Number: 20130701-5381.
    Comments Due: 5 p.m. ET 7/22/13.

    The filings are accessible in the Commission's eLibrary system by
clicking on the links or querying the docket number.
    Any person desiring to intervene or protest in any of the above
proceedings must file in accordance with Rules 211 and 214 of the
Commission's Regulations (18 CFR 385.211 and 385.214) on or before 5:00
p.m. Eastern time on the specified comment date. Protests may be
considered, but intervention is necessary to become a party to the
proceeding.
    eFiling is encouraged. More detailed information relating to filing
requirements, interventions, protests, service, and qualifying
facilities filings can be found at: http://www.ferc.gov/docs-filing/efiling/filing-req.pdf. For other information, call<PHONE_NUMBER>
(toll free). For TTY, call<PHONE_NUMBER>.

    Dated: July 2, 2013.
Nathaniel J. Davis, Sr.,
Deputy Secretary.
[FR Doc. 2013-16625 Filed 7-10-13; 8:45 am]
BILLING CODE 6717-01-P


[Federal Register Volume 88, Number 122 (Tuesday, June 27, 2023)]
[Rules and Regulations]
[Pages 41504-41506]
[FR Doc No: 2023-13591]

-----------------------------------------------------------------------

DEPARTMENT OF HOMELAND SECURITY

Coast Guard

33 CFR Part 165

[Docket Number USCG-2023-0234]
RIN 1625-AA00

Safety Zone; Fireworks Display, Great Egg Harbor Bay, Ocean City,
NJ

AGENCY: Coast Guard, DHS.

ACTION: Temporary final rule.

-----------------------------------------------------------------------

SUMMARY: The Coast Guard is establishing a temporary safety zone for
certain navigable waters of Great Egg Harbor Bay in Ocean City, NJ. The
safety zone is needed to protect personnel, vessels, and the marine
environment from potential hazards created by a barge-based fireworks
display. Entry of vessels or persons into this zone is prohibited
unless specifically authorized by the Captain of the Port (COTP)
Delaware Bay. Vessels within the zone prior to the enforcement period
must leave the zone before the enforcement period begins.

DATES: This rule is effective from 9 to 9:45 p.m. on July 29, 2023.

ADDRESSES: To view documents mentioned in this preamble as being
available in the docket, go to https://www.regulations.gov, type USCG-
2023-0234 in the search box and click ``Search.'' Next, in the Document
Type column, select ``Supporting & Related Material.''

FOR FURTHER INFORMATION CONTACT: If you have questions on this rule,
call or email Petty Officer Dylan Caikowski, Sector Delaware Bay,
Waterways Management Division, U.S. Coast Guard; telephone (215) 271-
4814, email [email protected].

SUPPLEMENTARY INFORMATION:

I. Table of Abbreviations

CFR Code of Federal Regulations
DHS Department of Homeland Security
FR Federal Register
NPRM Notice of proposed rulemaking
Sec.  Section
U.S.C. United States Code

II. Background Information and Regulatory History

    On February 16, 2023, Ocean City, New Jersey notified the Coast
Guard that it will be conducting a fireworks display from 9:15 to 9:30
p.m. on July 29, 2023. The fireworks are to be launched from a barge in
Great Egg Harbor Bay, in the vicinity of Rainbow Channel. In response,
on April 24, 2023, the Coast Guard published a notice of proposed
rulemaking (NPRM) titled Safety Zone; Delaware Bay, Lower Township, NJ.
There, we stated why we issued the NPRM and invited comments on our
proposed regulatory action related to this fireworks display. During
the comment period that ended May 24, 2023, we received one comment.

III. Legal Authority and Need for Rule

    The Coast Guard is issuing this rule under authority in 46 U.S.C.
70034 (previously 33 U.S.C. 1231). The COTP has determined that
potential hazards associated with a barge-based fireworks display will
be a safety concern for anyone within 600 feet of the fireworks barge.
The purpose of this rule is to ensure the safety of vessels and of
persons who might be in the navigable waters in the safety zone before,
during, and after a barge-based fireworks display.

IV. Discussion of Comments, Changes, and the Rule

    As noted above, we received one comment on our NPRM published April
24, 2023. The comment stated that the proposed creation of a safety
zone in Great Egg Harbor Bay, Ocean City, NJ, is justified based on the
government's compelling interest in protecting the safety of
individuals and the environment during a fireworks show, outweighing
the minimal restriction on individual freedom. There are no changes in
the regulatory text of this rule from the proposed rule in the NPRM.
    This rule establishes a temporary safety zone from 9 to 9:45 p.m.
on July 29, 2023. The safety zone will cover all navigable waters
within 600 feet of a barge in Great Egg Harbor Bay located at
approximate position latitude 39[deg]17'23.7'' N, longitude
074[deg]34'31.3'' W. The duration of the zone is intended to ensure the
safety of vessels and these navigable waters before, during, and after
the scheduled 9:15 to 9:30 p.m. fireworks display. No vessel or person
would be permitted to enter the safety zone without obtaining
permission from the COTP or a designated representative.

V. Regulatory Analyses

    We developed this rule after considering numerous statutes and
Executive orders related to rulemaking. Below we summarize our analyses
based on a number of these statutes and Executive orders, and we
discuss First Amendment rights of protestors.

A. Regulatory Planning and Review

    Executive Orders 12866 and 13563 direct agencies to assess the
costs and benefits of available regulatory alternatives and, if
regulation is necessary, to select regulatory approaches that maximize
net benefits. This rule has not been designated a ``significant
regulatory action,'' under section 3(f) of Executive Order 12866, as
amended by Executive Order 14094 (Modernizing Regulatory Review).
Accordingly, this rule has not been reviewed by the Office of
Management and Budget (OMB).
    This regulatory action determination is based on the following
factors: (1) although persons and vessels may not enter, transit
through, anchor in, or remain within the safety zone without
authorization from the COTP or a designated representative, they may
operate in the surrounding area during the enforcement period; (2)
persons and vessels will still be able to enter, transit through,
anchor in, or remain within the regulated area if authorized by the
COTP; and (3) the Coast Guard will provide advance notification of the
safety zone to the local maritime community by Local Notice to Mariners
and Broadcast Notice to Mariners.

B. Impact on Small Entities

    The Regulatory Flexibility Act of 1980, 5 U.S.C. 601-612, as
amended, requires Federal agencies to consider the potential impact of
regulations on small entities during rulemaking. The term ``small
entities'' comprises small businesses, not-for-profit organizations
that are independently owned and operated and are not dominant in their
fields, and governmental jurisdictions with populations of less than
50,000. The Coast Guard received no comments from the Small Business
Administration on this rulemaking. The Coast Guard certifies under 5
U.S.C. 605(b) that this rule will not have a significant economic
impact on a substantial number of small entities.
    While some owners or operators of vessels intending to transit the
safety zone may be small entities, for the reasons stated in section
V.A above, this rule will not have a significant economic impact on any
vessel owner or operator.
    Under section 213(a) of the Small Business Regulatory Enforcement
Fairness Act of 1996 (Pub. L. 104-121), we want to assist small
entities in understanding this rule. If the rule would affect your
small business, organization, or governmental jurisdiction and you have
questions concerning its provisions or options for compliance, please
call or email the person listed in the FOR FURTHER INFORMATION CONTACT
section.
    Small businesses may send comments on the actions of Federal
employees who enforce, or otherwise determine compliance with, Federal
regulations to the Small Business and Agriculture Regulatory
Enforcement Ombudsman and the Regional Small Business Regulatory
Fairness Boards. The Ombudsman evaluates these actions annually and
rates each agency's responsiveness to small business. If you wish to
comment on actions by employees of the Coast Guard, call 1-888-REG-FAIR
(1-888-734-3247). The Coast Guard will not retaliate against small
entities that question or complain about this rule or any policy or
action of the Coast Guard.

C. Collection of Information

    This rule will not call for a new collection of information under
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

D. Federalism and Indian Tribal Governments

    A rule has implications for federalism under Executive Order 13132,
Federalism, if it has a substantial direct effect on the States, on the
relationship between the National Government and the States, or on the
distribution of power and responsibilities among the various levels of
government. We have analyzed this rule under that Order and have
determined that it is consistent with the fundamental federalism
principles and preemption requirements described in Executive Order
13132.
    Also, this rule does not have tribal implications under Executive
Order 13175, Consultation and Coordination with Indian Tribal
Governments, because it does not have a substantial direct effect on
one or more Indian tribes, on the relationship between the Federal
Government and Indian tribes, or on the distribution of power and
responsibilities between the Federal Government and Indian tribes.

E. Unfunded Mandates Reform Act

    The Unfunded Mandates Reform Act of 1995 (2 U.S.C. 1531-1538)
requires Federal agencies to assess the effects of their discretionary
regulatory actions. In particular, the Act addresses actions that may
result in the expenditure by a State, local, or tribal government, in
the aggregate, or by the private sector of $100,000,000 (adjusted for
inflation) or more in any one year. Though this rule will not result in
such an expenditure, we do discuss the effects of this rule elsewhere
in this preamble.

F. Environment

    We have analyzed this rule under Department of Homeland Security
Directive 023-01, Rev. 1, associated implementing instructions, and
Environmental Planning COMDTINST 5090.1 (series), which guide the Coast
Guard in complying with the National Environmental Policy Act of 1969
(42 U.S.C. 4321-4370f), and have determined that this action is one of
a category of actions that do not individually or cumulatively have a
significant effect on the human environment. This rule involves a
temporary safety zone lasting 45 minutes that would prohibit entry
within 600 feet of a fireworks barge. It is categorically excluded from
further review under paragraph L60(a) of Appendix A, Table 1 of DHS
Instruction Manual 023-01-001-01, Rev. 1. A Record of Environmental
Consideration supporting this determination is available in the docket.
For instructions

on locating the docket, see the ADDRESSES section of this preamble.

G. Protest Activities

    The Coast Guard respects the First Amendment rights of protesters.
Protesters are asked to call or email the person listed in the FOR
FURTHER INFORMATION CONTACT section to coordinate protest activities so
that your message can be received without jeopardizing the safety or
security of people, places or vessels.

List of Subjects in 33 CFR Part 165

    Harbors, Marine safety, Navigation (water), Reporting and
recordkeeping requirements, Security measures, Waterways.
    For the reasons discussed in the preamble, the Coast Guard amends
33 CFR part 165 as follows:

PART 165--REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS

0
1. The authority citation for part 165 continues to read as follows:

    Authority:  46 U.S.C. 70034, 70051, 70124; 33 CFR 1.05-1, 6.04-
1, 6.04-6, and 160.5; Department of Homeland Security Delegation No.
00170.1, Revision No. 01.3.

0
2. Add Sec.  165.T05-0234 to read as follows:

Sec.  165.T05-0234  Safety Zone; Fireworks Display, Great Egg Harbor
Bay, Ocean City, NJ.

    (a) Location. All navigable waters within 600 feet of a barge in
Great Egg Harbor Bay located at approximate position latitude
39[deg]17'23.7'' N, longitude 074[deg]34'31.3'' W.
    (b) Definitions. As used in this section, designated representative
means a Coast Guard Patrol Commander, including a Coast Guard petty
officer, warrant or commissioned officer on board a Coast Guard vessel
or on board a federal, state, or local law enforcement vessel assisting
the Captain of the Port (COTP), Sector Delaware Bay in the enforcement
of the safety zone.
    (c) Regulations.
    (1) Under the general safety zone regulations in subpart C of this
part, you may not enter or remain in the safety zone described in
paragraph (a) of this section unless authorized by the COTP or the
COTP's designated representative.
    (2) To seek permission to enter or remain in the zone, contact the
COTP or the COTP's representative via VHF-FM channel 16 or 215-271-
4807. Those in the safety zone must comply with all lawful orders or
directions given to them by the COTP or the COTP's designated
representative.
    (3) No vessel authorized to enter or remain in the zone may take on
bunkers or conduct lightering operations within the safety zone during
its enforcement period.
    (4) This section applies to all vessels except those engaged in law
enforcement, aids to navigation servicing, and emergency response
operations.
    (d) Enforcement. The U.S. Coast Guard may be assisted in the patrol
and enforcement of the safety zone by Federal, State, and local
agencies.
    (e) Enforcement period. This zone will be enforced from
approximately 9 to 9:45 p.m. on July 29, 2023.

    Dated: June 21, 2023.
Kate F. Higgins-Bloom,
Captain, U.S. Coast Guard, Captain of the Port, Sector Delaware Bay.
[FR Doc. 2023-13591 Filed 6-26-23; 8:45 am]
BILLING CODE 9110-04-P