[Federal Register: August 7, 2008 (Volume 73, Number 153)]
[Proposed Rules]
[Page 45893-45895]
[DOCID:fr07au08-16]

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DEPARTMENT OF TRANSPORTATION

Federal Aviation Administration

14 CFR Part 39

[Docket No. FAA-2008-0847; Directorate Identifier 2008-NM-056-AD]
RIN 2120-AA64

Airworthiness Directives; Boeing Model 777 Airplanes

AGENCY: Federal Aviation Administration (FAA), DOT.

ACTION: Notice of proposed rulemaking (NPRM).

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SUMMARY: We propose to adopt a new airworthiness directive (AD) for
certain Boeing Model 777 airplanes. This proposed AD would require
doing an inspection of the motor operated valve (MOV) actuators of the
main and center fuel tanks for a certain part number; replacing the MOV
actuator with a new MOV actuator if necessary; and measuring the
electrical resistance of the bond from the adapter plate to the
airplane structure, and corrective actions if necessary. This proposed
AD would also require revising the Airworthiness Limitations section of
the Instructions for Continued Airworthiness. This proposed AD results
from fuel system reviews conducted by the manufacturer. We are
proposing this AD to prevent electrical current from flowing through a
MOV actuator into a fuel tank, which could create a potential ignition
source inside the fuel tank. This condition, in combination with
flammable fuel vapors, could result in a fuel tank explosion and
consequent loss of the airplane.

DATES: We must receive comments on this proposed AD by September 22,
2008.

ADDRESSES: You may send comments by any of the following methods:
     Federal eRulemaking Portal: Go to http://
www.regulations.gov. Follow the instructions for submitting comments.
     Fax:<PHONE_NUMBER>.
     Mail: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590.
     Hand Delivery: U.S. Department of Transportation, Docket
Operations, M-30, West Building Ground Floor, Room W12-140, 1200 New
Jersey Avenue, SE., Washington, DC 20590, between 9 a.m. and 5 p.m.,
Monday through Friday, except Federal holidays.
    For service information identified in this AD, contact Boeing
Commercial Airplanes, P.O. Box 3707, Seattle, Washington 98124-2207.

Examining the AD Docket

    You may examine the AD docket on the Internet at http://
www.regulations.gov; or in person at the Docket Management Facility
between 9 a.m. and 5 p.m., Monday through Friday, except Federal
holidays. The AD docket contains this proposed AD, the regulatory
evaluation, any comments received, and other information. The street
address for the Docket Office (telephone<PHONE_NUMBER>) is in the
ADDRESSES section. Comments will be available in the AD docket shortly
after receipt.

FOR FURTHER INFORMATION CONTACT: Margaret Langsted, Aerospace Engineer,
Propulsion Branch, ANM-140S, FAA, Seattle Aircraft Certification
Office, 1601 Lind Avenue, SW., Renton, Washington 98057-3356; telephone
(425) 917-6500; fax<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

Comments Invited

    We invite you to send any written relevant data, views, or
arguments about this proposed AD. Send your comments to an address
listed under the ADDRESSES section. Include ``Docket No. FAA-2008-0847;
Directorate Identifier 2008-NM-056-AD'' at the beginning of your
comments. We specifically invite comments on the overall regulatory,
economic, environmental, and energy aspects of this proposed AD. We
will consider all comments received by the closing date and may amend
this proposed AD because of those comments.
    We will post all comments we receive, without change, to http://
www.regulations.gov, including any personal information you provide. We
will also post a report summarizing each substantive verbal contact we
receive about this proposed AD.

Discussion

    The FAA has examined the underlying safety issues involved in fuel
tank explosions on several large transport airplanes, including the
adequacy of existing regulations, the service history of airplanes
subject to those regulations, and existing maintenance practices for
fuel tank systems. As a result of those findings, we issued a
regulation titled ``Transport Airplane Fuel Tank System Design Review,
Flammability Reduction and Maintenance and Inspection Requirements''
(66 FR 23086, May 7, 2001). In addition to new airworthiness standards
for transport airplanes and new maintenance requirements, this rule
included Special Federal Aviation Regulation No. 88 (``SFAR 88,''
Amendment 21-78, and subsequent Amendments 21-82 and 21-83).
    Among other actions, SFAR 88 requires certain type design (i.e.,
type certificate (TC) and supplemental type certificate (STC)) holders
to substantiate that their fuel tank systems can prevent ignition
sources in the fuel tanks. This requirement applies to type design
holders for large turbine-powered transport airplanes and for
subsequent modifications to those airplanes. It requires them to
perform design reviews and to develop design changes and maintenance
procedures if their designs do not meet the new fuel tank safety
standards. As explained in the preamble to the rule, we intended to
adopt airworthiness directives to mandate any changes found necessary
to address unsafe conditions identified as a result of these reviews.
    In evaluating these design reviews, we have established four
criteria intended to define the unsafe conditions associated with fuel
tank systems that require corrective actions. The percentage of
operating time during which fuel tanks are exposed to flammable
conditions is one of these criteria. The other three criteria address
the failure types under evaluation: single failures, single failures in
combination with a latent condition(s), and in-service failure
experience. For all four criteria, the evaluations included
consideration of previous actions taken

that may mitigate the need for further action.
    We have determined that the actions identified in this AD are
necessary to reduce the potential of ignition sources inside fuel
tanks, which, in combination with flammable fuel vapors, could result
in fuel tank explosions and consequent loss of the airplane.
    Boeing has found that, under specific conditions, it is possible
for electrical current to flow through a motor operated valve (MOV)
actuator into a fuel tank, which could create a potential ignition
source inside the fuel tank. This condition, if not corrected, in
combination with flammable fuel vapors, could result in a fuel tank
explosion and consequent loss of the airplane.

Other Related Rulemaking

    On May 14, 2008, we issued AD 2008-11-13, amendment 39-15536 (73 FR
30737, May 29, 2008), applicable to certain Boeing Model 777-200, -
200LR, -300, and -300ER series airplanes. That AD requires revising the
Airworthiness Limitations (AWLs) section of the Instructions for
Continued Airworthiness (ICA) by incorporating new limitations for fuel
tank systems to satisfy SFAR 88 requirements. That AD also requires the
initial performance of certain repetitive inspections specified in the
AWLs to phase in those inspections, and repair if necessary. That AD
resulted from a design review of the fuel tank systems. We issued that
AD to prevent the potential for ignition sources inside fuel tanks
caused by latent failures, alterations, repairs, or maintenance
actions, which, in combination with flammable fuel vapors, could result
in fuel tank explosions and consequent loss of the airplane.
Incorporating AWL No. 28-AWL-19 and No. 28-AWL-20 into the AWLs section
of the ICA in accordance with paragraph (g)(2) of AD 2008-11-13,
terminates the action required by paragraph (h) of this AD.

Relevant Service Information

    We have reviewed Boeing Alert Service Bulletin 777-28A0034, dated
August 2, 2007. The service bulletin describes procedures for doing an
inspection of the MOV actuators of the main and center fuel tanks for a
certain part number; replacing the MOV actuator with a new MOV actuator
if necessary; and measuring the electrical resistance of the bond from
the adapter plate to the airplane structure, and corrective actions if
necessary. The corrective actions include reworking the bracket,
cleaning and refinishing the bracket area, removing and reworking the
index plate, and electrically bonding and installing the index plate.
    We have also reviewed Section 9, Revision 28, dated February 2006,
of Boeing 777 Maintenance Planning Data (MPD) Document, D622W001-9
(hereafter referred to as ``Boeing 777 MPD''). Subsection E of Section
9 of the Boeing 777 MPD adds new AWLs No. 28-AWL-19 and No. 28-AWL-20,
which are critical design configuration control limitations (CDCCLs) to
address inspection and repair of the MOV actuators.

FAA's Determination and Requirements of this Proposed AD

    We are proposing this AD because we evaluated all relevant
information and determined the unsafe condition described previously is
likely to exist or develop in other products of the(se) same type
design(s). This proposed AD would require accomplishing the actions
specified in the service information described previously.

Costs of Compliance

    We estimate that this proposed AD would affect 197 airplanes of
U.S. registry. We also estimate that it would take about 352 or 452
work-hours per product to comply with this proposed AD, depending on
the product configuration. The average labor rate is $80 per work-hour.
Based on these figures, we estimate the cost of this proposed AD to the
U.S. operators to be $5,547,520 to $7,123,520, or $28,160 to $36,160
per product, depending on the product configuration.

Authority for this Rulemaking

    Title 49 of the United States Code specifies the FAA's authority to
issue rules on aviation safety. Subtitle I, section 106, describes the
authority of the FAA Administrator. ``Subtitle VII: Aviation
Programs,'' describes in more detail the scope of the Agency's
authority.
    We are issuing this rulemaking under the authority described in
``Subtitle VII, Part A, Subpart III, Section 44701: General
requirements.'' Under that section, Congress charges the FAA with
promoting safe flight of civil aircraft in air commerce by prescribing
regulations for practices, methods, and procedures the Administrator
finds necessary for safety in air commerce. This regulation is within
the scope of that authority because it addresses an unsafe condition
that is likely to exist or develop on products identified in this
rulemaking action.

Regulatory Findings

    We determined that this proposed AD would not have federalism
implications under Executive Order 13132. This proposed AD would not
have 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.
    For the reasons discussed above, I certify this proposed
regulation:
    1. Is not a ``significant regulatory action'' under Executive Order
12866,
    2. Is not a ``significant rule'' under the DOT Regulatory Policies
and Procedures (44 FR 11034, February 26, 1979), and
    3. Will not have a significant economic impact, positive or
negative, on a substantial number of small entities under the criteria
of the Regulatory Flexibility Act.
    You can find our regulatory evaluation and the estimated costs of
compliance in the AD Docket.

List of Subjects in 14 CFR Part 39

    Air transportation, Aircraft, Aviation safety, Safety.

The Proposed Amendment

    Accordingly, under the authority delegated to me by the
Administrator, the FAA proposes to amend 14 CFR part 39 as follows:

PART 39--AIRWORTHINESS DIRECTIVES

    1. The authority citation for part 39 continues to read as follows:

    Authority: 49 U.S.C. 106(g), 40113, 44701.

Sec.  39.13  [Amended]

    2. The FAA amends Sec.  39.13 by adding the following new AD:

Boeing: Docket No. FAA-2008-0847; Directorate Identifier 2008-NM-
056-AD.

Comments Due Date

    (a) We must receive comments by September 22, 2008.

Affected ADs

    (b) None.

Applicability

    (c) This AD applies to Boeing Model 777-200, -200LR, -300, and -
300ER series airplanes, certificated in any category; as identified
in Boeing Alert Service Bulletin 777-28A0034, dated August 2, 2007.

    Note 1: This AD requires revisions to certain operator
maintenance documents to include new inspections. Compliance with
these inspections is required by 14 CFR 91.403(c). For airplanes
that have been previously modified, altered, or repaired in the
areas addressed by these inspections, the operator may not be able
to accomplish the

inspections described in the revisions. In this situation, to comply
with 14 CFR 91.403(c), the operator must request approval for an
alternative method of compliance (AMOC) according to paragraph (k)
of this AD. The request should include a description of changes to
the required inspections that will ensure the continued operational
safety of the airplane.

Unsafe Condition

    (d) This AD results from fuel system reviews conducted by the
manufacturer. We are issuing this AD to prevent electrical current
from flowing through a motor operated valve (MOV) actuator into a
fuel tank, which could create a potential ignition source inside the
fuel tank. This condition, in combination with flammable fuel
vapors, could result in a fuel tank explosion and consequent loss of
the airplane.

Compliance

    (e) Comply with this AD within the compliance times specified,
unless already done.

Inspection

    (f) Within 60 months after the effective date of this AD, do an
inspection of the MOV actuators of the main and center fuel tanks
for part number MA20A1001-1, in accordance with the Accomplishment
Instructions of Boeing Alert Service Bulletin 777-28A0034, dated
August 2, 2007.

Replacement

    (g) If any part number MA20A1001-1 is found during the
inspection required by paragraph (f) of this AD, within 60 months
after the effective date of this AD, do the actions specified in
paragraphs (g)(1) and (g)(2) of this AD by accomplishing all the
applicable actions specified in the Accomplishment Instructions of
Boeing Alert Service Bulletin 777-28A0034, dated August 2, 2007. Do
all applicable corrective actions before further flight.
    (1) Replace the MOV actuator with a new MOV actuator, part
number MA030A1001.
    (2) Measure the electrical resistance of the bond from the
adapter plate to the airplane structure, and do all applicable
corrective actions.

Airworthiness Limitations (AWLs): Revision for AWL No. 28-AWL-19 and
28-AWL-20

    (h) Concurrently with accomplishing the actions required by
paragraph (g) of this AD, revise the AWLs section of the
Instructions for Continued Airworthiness (ICA) by incorporating AWL
No. 28-AWL-19 and No. 28-AWL-20 of Subsection E of Section 9,
Revision 28, dated February 2006, of the Boeing 777 Maintenance
Planning Data (MPD) Document, D622W001-9.

No Alternative Critical Design Configuration Control Limitations
(CDCCLs)

    (i) After accomplishing the action specified in paragraph (h) of
this AD, no alternative CDCCLs may be used unless the CDCCLs are
approved as an AMOC in accordance with the procedures specified in
paragraph (k) of this AD.

Terminating Action for AWLs Revision

    (j) Incorporating AWL No. 28-AWL-19 and No. 28-AWL-20 into the
AWLs section of the ICA in accordance with paragraph (g)(2) of AD
2008-11-13, amendment 39-15536, terminates the action required by
paragraph (h) of this AD.

Alternative Methods of Compliance (AMOCs)

    (k)(1) The Manager, Seattle ACO, FAA, ATTN: Margaret Langsted,
Aerospace Engineer, Propulsion Branch, ANM-140S, FAA, SACO, 1601
Lind Avenue, SW., Renton, Washington 98057-3356; telephone (425)
917-6500; fax<PHONE_NUMBER>; has the authority to approve AMOCs for
this AD, if requested using the procedures found in 14 CFR 39.19.
    (2) To request a different method of compliance or a different
compliance time for this AD, follow the procedures in 14 CFR 39.19.
Before using any approved AMOC on any airplane to which the AMOC
applies, notify your appropriate principal inspector (PI) in the FAA
Flight Standards District Office (FSDO), or lacking a PI, your local
FSDO.

    Issued in Renton, Washington, on July 29, 2008.
Ali Bahrami,
Manager, Transport Airplane Directorate, Aircraft Certification
Service.
[FR Doc. E8-18211 Filed 8-6-08; 8:45 am]

BILLING CODE 4910-13-P


[Federal Register: November 4, 2010 (Volume 75, Number 213)]
[Notices]
[Page 67983-67984]
[DOCID:fr04no10-51]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2010-N-0536]

Agency Information Collection Activities: Proposed Collection;
Comment Request, Guidance for Industry on Pharmacogenomic Data
Submissions; Extension

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing an
opportunity for public comment on the proposed collection of certain
information by the agency. Under the Paperwork Reduction Act of 1995
(the PRA), Federal agencies are required to publish notice in the
Federal Register concerning each proposed collection of information,
including each proposed extension of an existing collection of
information, and to allow 60 days for public comment in response to the
notice. This notice solicits comments on the information collection
resulting from recommendations to sponsors submitting or holding
investigational new drug applications (INDs), new drug applications
(NDAs), or biologic licensing applications (BLAs) on what
pharmacogenomic data should be submitted to the agency during the drug
development process.

DATES: Submit either electronic or written comments on the collection
of information by January 3, 2011.

ADDRESSES: Submit electronic comments on the collection of information
to http://www.regulations.gov. Submit written comments on the
collection of information to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. All comments should be identified with the docket
number found in brackets in the heading of this document.

FOR FURTHER INFORMATION CONTACT: Elizabeth Berbakos, Office of
Information Management, Food and Drug Administration, 1350 Piccard Dr.,
PI50-400B, Rockville, MD 20850,<PHONE_NUMBER>,
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Under the PRA (44 U.S.C. 3501-3520), Federal
agencies must obtain approval from the Office of Management and Budget
(OMB) for each collection of information they conduct or sponsor.
``Collection of information'' is defined in

44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes agency requests or
requirements that members of the public submit reports, keep records,
or provide information to a third party. Section 3506(c)(2)(A) of the
PRA (44 U.S.C. 3506(c)(2)(A)) requires Federal agencies to provide a
60-day notice in the Federal Register concerning each proposed
collection of information, including each proposed extension of an
existing collection of information, before submitting the collection to
OMB for approval. To comply with this requirement, FDA is publishing
notice of the proposed collection of information set forth in this
document.
    With respect to the following collection of information, FDA
invites comments on these topics: (1) Whether the proposed collection
of information is necessary for the proper performance of FDA's
functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.

Guidance for Industry on Pharmacogenomic Data Submissions (OMB Control
Number 0910-0557--Extension)

    The guidance provides recommendations to sponsors submitting or
holding INDs, NDAs, or BLAs on what pharmacogenomic data should be
submitted to the agency during the drug development process. Sponsors
holding and applicants submitting INDs, NDAs, or BLAs are subject to
FDA requirements for submitting to the agency data relevant to drug
safety and efficacy (Sec. Sec.  312.22, 312.23, 312.31, 312.33, 314.50,
314.81, 601.2, and 601.12).
    The guidance interprets FDA regulations for IND, NDA, or BLA
submissions, clarifying when the regulations require pharmacogenomics
data to be submitted and when the submission of such data is voluntary.
The pharmacogenomic data submissions described in the guidance that are
required to be submitted to an IND, NDA, BLA, or annual report are
covered by the information collection requirements under parts 312,
314, and 601 (21 CFR parts 312, 314, and 601) and are approved by OMB
under control numbers 0910-0014 (part 312--INDs); 0910-0001 (part 314--
NDAs and annual reports); and 0910-0338 (part 601--BLAs).
    The guidance distinguishes between pharmacogenomic tests that may
be considered valid biomarkers appropriate for regulatory decision-
making, and other, less well-developed exploratory tests. The
submission of exploratory pharmacogenomic data is not required under
the regulations, although the agency encourages the voluntary
submission of such data.
    The guidance describes the voluntary genomic data submission (VGDS)
that can be used for such a voluntary submission. The guidance does not
recommend a specific format for the VGDS, except that such a voluntary
submission be designated as a VGDS. The data submitted in a VGDS and
the level of detail should be sufficient for FDA to be able to
interpret the information and independently analyze the data, verify
results, and explore possible genotype-phenotype correlations across
studies. FDA does not want the VGDS to be overly burdensome and time-
consuming for the sponsor.
    FDA has estimated the burden of preparing a voluntary submission
described in the guidance that should be designated as a VGDS. Based on
FDA's experience with this guidance over the past few years, and on
FDA's familiarity with sponsors' interest in submitting pharmacogenomic
data during the drug development process, FDA estimates that
approximately seven sponsors will submit approximately one VGDS and
that, on average, each VGDS will take approximately 50 hours to prepare
and submit to FDA.
    FDA estimates the burden of this collection of information as
follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
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                                                                                Annual
                                                                        Number of      frequency  per    Total annual      Hours per       Total hours
                                                                       respondents        response        responses         response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Voluntary Genomic Data Submissions Total...........................               7                1                7               50              350
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\1\ There are no capital costs or operating and maintenance costs associated with this collection.

    Dated: October 29, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-27847 Filed 11-3-10; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register: March 13, 2007 (Volume 72, Number 48)]
[Notices]
[Page 11408-11409]
[DOCID:fr13mr07-88]

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SECURITIES AND EXCHANGE COMMISSION

[Investment Company Act Release No. 27748; 812-13238]

Hercules Technology Growth Capital, Inc., et al.; Notice of
Application

March 7, 2007.
AGENCY: Securities and Exchange Commission (the ``Commission'').

ACTION: Notice of an application for an order under sections 6(c),
57(c), and 57(i) of the Investment Company Act of 1940 (the ``Act'')
and rule 17d-1 thereunder granting exemptions from sections 18(a),
57(a)(1), 57(a)(2) and 61(a) of the Act and permitting certain
transactions otherwise prohibited by section 57(a)(4) of the Act.

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Summary of Application: Applicants, Hercules Technology Growth Capital,
Inc. (``HTGC''), Hercules Technology II, L.P. (``HTII''), Hercules
Technology SBIC Management, LLC (``HTM''), Hercules Funding I, LLC
(``HFI'') and Hercules Funding Trust I (``HFT''), hereby apply for an
order permitting a business development company and its wholly-owned
subsidiaries to engage in certain transactions that otherwise would be
permitted if the business development company and its subsidiaries were
one company, and permitting the business development company to adhere
to a modified asset coverage requirement.

Filing Dates: The application was filed on September 28, 2005 and
amended on March 5, 2007.

Hearing or Notification of Hearing: An order granting the application
will be issued unless the Commission orders a hearing. Interested
persons may request a hearing by writing to the Commission's Secretary
and serving applicants with a copy of the request, personally or by
mail. Hearing requests should be received by the Commission by 5:30
p.m. on April 2, 2007, and should be accompanied by proof of service on
applicants, in the form of an affidavit or, for lawyers, a certificate
of service. Hearing requests should state the nature of the writer's
interest, the reason for the request, and the issues contested. Persons
who wish to be notified of a hearing may request notification by
writing to the Commission's Secretary.

ADDRESSES: Secretary, U.S. Securities and Exchange Commission, 100 F
Street, NE., Washington, DC 20549-1090. Applicants, c/o Manuel A.
Henriquez, Chairman, President and Chief Executive Officer, Hercules
Technology Growth Capital, Inc., 525 University Avenue, Suite 700, Palo
Alto, CA 94301.

FOR FURTHER INFORMATION CONTACT: Emerson S. Davis, Sr., Senior Counsel,
at<PHONE_NUMBER>, or Nadya B. Roytblat, Assistant Director, at (202)
551-6821 (Division of Investment Management, Office of Investment
Company Regulation).

SUPPLEMENTARY INFORMATION: The following is a summary of the
application. The complete application is available for a fee at the
Commission's Public Reference Branch, 100 F Street, NE., Washington, DC
20549-0102 (tel.<PHONE_NUMBER>).

Applicants' Representations

    1. HTGC, a Maryland corporation, is a closed-end, non-diversified
management investment company that has elected to be regulated as a
business development company (``BDC'') within the meaning of section
2(a)(48) of the Act.\1\ HTGC is a specialty finance company that
provides debt and equity capital to technology-related and life-science
companies at all stages of development. HTGC's business and affairs are
managed under the direction of its board of directors (``Board'').
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    \1\ Section 2(a)(48) defines a BDC to be any closed-end
investment company that operates for the purpose of making
investments in securities described in sections 55(a)(1) through
55(a)(3) of the Act and makes available significant managerial
assistance with respect to the issuers of such securities.
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    2. HTII, a Delaware limited partnership and a wholly-owned
subsidiary of HTGC, is a small business investment company (``SBIC'')
licensed under the Small Business Administration (``SBA'') to operate
under the Small Business Investment Act of 1958 (``SBIA''). HTII relies
on section 3(c)(7) of the Act. HTM, a Delaware limited liability
company and a wholly-owned subsidiary of HTGC, is the general partner
and investment adviser to HTII. HTGC is the primary limited partner of
HTII. Manuel A. Henriquez, an officer of HTGC, and H. Scott Harvey, an
officer of HTGC, each have a nominal (0.001%) limited partnership
investment in HTII pursuant to the advice of tax counsel in order to
ensure that HTII is taxed as a partnership under the Internal Revenue
Code of 1986, as amended. HFI, a Delaware limited liability company,
and HFT, a Delaware statutory trust, and each wholly-owned subsidiary
of HTGC, were created to facilitate debt financing collateralized by
certain HTGC's investments. HFT relies on rule 3a-7 under the Act. HFT
is a wholly-owned subsidiary of HFI.
    3. Applicants may in the future establish additional wholly-owned
subsidiaries of HTGC, (together with HTII, HTM, HFI and HFT,
``Subsidiaries''), private investment companies that rely on section
3(c)(7) of the Act and some of which may be licensed by the SBA to
operate under the SBIA as SBICs (together with HTII, ``SBIC
Subsidiaries'').

Applicant's Legal Analysis

    1. Applicants request an exemption pursuant to sections 6(c), 57(c)
and 57(i) of the Act and rule 17d-1 under the Act from the provisions
of sections 18(a), 57(a)(1), 57(a)(2) and 61(a) of the Act to permit
HTGC and the Subsidiaries to engage in certain transactions that
otherwise would be permitted if HTGC and the Subsidiaries were one
company and to permit HTGC to adhere a modified asset coverage
requirement.
    2. Section 18(a) of the Act prohibits a registered closed-end
investment company from issuing any class of senior security or selling
any such security of which it is the issuer unless the company complies
with the asset coverage requirements set forth in that section. Section
61(a) of the Act makes section 18 applicable to BDCs, with certain
modifications. Section 18(k) exempts an investment company operating as
an SBIC from the asset coverage requirements for senior securities
representing indebtedness that are contained in sections 18(a)(1)(A)
and (B).
    3. Applicants state that a question exists as to whether HTGC must
comply with the asset coverage requirements of Section 18(a) (as
modified by Section 61(a)) solely on an individual basis or whether
HTGC must also comply with the asset coverage requirements on a
consolidated basis because HTGC may be deemed to be an indirect issuer
of any class of senior securities issued by HTII or another SBIC
Subsidiary. Applicants state that they wish to treat

HTII and other SBIC Subsidiaries as if each was a BDC subject to
sections 18 and 61 of the Act. Applicants state that companies
operating under the SBIA, such as HTII, will be subject to the SBA's
substantial regulation of permissible leverage in its capital
structure.
    4. Section 6(c) of the Act, in relevant part, permits the
Commission to exempt any transaction or class of transactions from any
provision of the Act if, and to the extent that, such exemption is
necessary or appropriate in the public interest and consistent with the
protection of investors and the purposes fairly intended by the policy
and provisions of the Act. Applicants state that the requested relief
satisfies the section 6(c) standard. Applicants contend that, to the
extent that HTGC is entitled to rely on section 18(k) for an exemption
from the asset coverage requirements of sections 18(a) and 61(a), there
is no policy reason to deny the benefit of that exemption when HTGC
consolidates its assets with those of HTII and other SBIC Subsidiaries
for the purpose of compliance with those requirements.
    5. Sections 57(a)(1) and (2) of the Act generally prohibit, with
certain exceptions, sales or purchases or other property between BDCs
and certain of their affiliates as described in section 57(b) of the
Act. Section 57(b) includes a person, directly or indirectly, either
controlling, controlled by or under common control of the BDC.
Applicants state that HTGC owns or will directly or indirectly own more
than 99.9% of the voting securities of each Subsidiary and each
Subsidiary is or will be under the common control of HTGC. Applicants
further state that any purchase and sales between (a) HTGC and one or
more Subsidiaries, (b) Subsidiaries and downstream controlled
affiliates of HTGC and another Subsidiary and (c) HTGC and a controlled
portfolio affiliate of a Subsidiary may be prohibited. Applicants
submit that the requested relief is to the extent to permit HTGC and
its Subsidiaries, all of whom are owned, directly or indirectly, by the
shareholders of HTGC, to do that which they would otherwise would be
permitted to do if they were one company.
    6. Section 57(c) provides that the Commission will exempt a
proposed transaction from the terms of the proposed transactions,
including the consideration to be paid or received, if they are
reasonable and fair and do not involve overreaching of any person
concerned, and the proposed transaction is consistent with the policy
of the business development company concerned and the general purposes
of the Act. Applicants submit that the requested relief meets this
standard.
    7. Section 17(d) of the Act and rule 17d-1 under the Act prohibit
persons of registered investment company, or an affiliated person of
such person, acting as principal, from participating in any joint
transaction or arrangement in which the registered company or a company
it controls is a participant, unless the Commission has issued an order
authorizing the arrangement. Section 57(a)(4) of the Act imposes
substantially the same prohibitions on joint transactions involving
BDCs and certain affiliates of their affiliates as described in section
57(b). Section 57(i) of the Act provides that rules and regulations
under sections 17(a) and (d) and rule 17d-1 will apply to transactions
subject to section 57(a)(4) in the absence of rules under the section.
The Commission has not adopted rules under section 57(a)(4) with
respect to joint transactions and, accordingly, the standard set forth
in rule 17d-1 governs applicants' request for relief.
    8. Applicants state that a joint transaction in which a Subsidiary
and HTGC or another Subsidiary may be prohibited under section 57(a)(4)
because HTGC would not be a controlled affiliate of the Subsidiaries.
Applicants request relief under section 57(i) and rule 17d-1 to permit
joint transactions in which the Subsidiaries to the extent that such
transactions would not be prohibited if the Subsidiaries participating
in the transactions were deemed to be part of HTGC and not separate
companies.
    9. In determining whether to grant an order under section 57(i) and
rule 17d-1, the Commission may consider whether the participation of
the BDC in the joint transaction is consistent with the provisions,
policies, and purposes of the Act to the extent to which such
participation is on a basis different from or less advantageous than
that of other participants in the transaction. Applicants state that
the standard is satisfied because the requested relief would be simply
to permit HTGC and its Subsidiaries to conduct their business as if
they were one company.

Applicants' Conditions

    Applicants agree that any order granting the requested relief will
be subject to the following conditions:
    1. Except for a nominal limited partnership interest in a
Subsidiary to the extent necessary to accomplish the Subsidiary's
taxation goals as described in this Application, HTGC will at all times
be the sole limited partner of any Subsidiary and the sole owner of the
Subsidiary's general partner, or otherwise own and hold beneficially,
all of the outstanding voting securities or other equity interests in
the Subsidiary.
    2. No person shall serve or act as investment adviser to HTII or
another Subsidiary unless the HTGC Board and shareholders of HTGC have
taken the action with respect thereto also required to be taken by the
functional equivalent of the board of directors of HTII or another
Subsidiary and shareholders of HTII or another Subsidiary as if HTII or
another Subsidiary were a BDC.
    3. No person shall serve as managing member of HTM unless such
person also shall be a member of the management of HTGC. The managing
members of HTM will be elected or appointed by HTGC.
    4. HTGC will not issue or sell any senior security and HTGC will
not cause or permit HTII or any other SBIC Subsidiary to issue or sell
any senior security of which HTGC, HTII or any other SBIC Subsidiary is
the issuer except to the extent permitted by section 18 (as modified
for BDCs by section 61) of the Act; provided that immediately after
issuance or sale by any HTGC, HTII or any other SBIC Subsidiary of any
such senior security, HTGC individually and on a consolidated basis,
shall have the asset coverage required by section 18(a) of the Act (as
modified by section 61(a)), except that, in determining whether HTGC on
a consolidated basis has the asset coverage required by section 18(a)
of the Act (as modified by section 61(a)), any senior securities
representing indebtedness of HTII or another SBIC Subsidiary shall not
be considered senior securities and, for purposes of the definition of
``asset coverage'' in section 18(h), will be treated as indebtedness
not represented by senior securities.

    For the Commission, by the Division of Investment Management,
pursuant to delegated authority.
Florence E. Harmon,
Deputy Secretary.
[FR Doc. E7-4521 Filed 3-12-07; 8:45 am]

BILLING CODE 8010-01-P


[Federal Register Volume 85, Number 228 (Wednesday, November 25, 2020)]
[Notices]
[Pages 75331-75334]
[FR Doc No: 2020-26133]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

Termination of the Food and Drug Administration's Unapproved
Drugs Initiative; Request for Information Regarding Drugs Potentially
Generally Recognized as Safe and Effective

AGENCY: Food and Drug Administration (FDA), Department of Health and
Human Services (HHS).

ACTION: Notice; request for information.

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SUMMARY: The Department of Health and Human Services is issuing this
Notice to withdraw FDA's Marketed Unapproved Drugs--Compliance Policy
Guide, Sec. 440.100, Marketed New Drugs Without Approved NDAs or ANDAs,
and to request information from the public regarding drugs that may be
grandfathered or generally recognized as safe and effective.

DATES: Part I of this Notice shall be effective thirty days from the
date of publication in the Federal Register. To be considered,
responses and comments related to Part II of this Notice must be
received electronically at the email

address listed below. The Department will consider information
submitted by the public in response to Part II of this Notice on a
rolling basis, and until further notice.

ADDRESSES: Responses to Part II must be submitted electronically, and
should be addressed to<EMAIL_ADDRESS>In the subject line of the email
message, submissions should include ``GRASE RFI Response.''

FOR FURTHER INFORMATION CONTACT: Nick Uehlecke, 200 Independence Ave.
SW, Washington, DC 20201; or by email at<EMAIL_ADDRESS>or by
telephone at 1-877-696-6775.

SUPPLEMENTARY INFORMATION: The Trump Administration, through the
Department of Health and Human Services (HHS), is continuing its
efforts to reduce the price of prescription drugs. This Notice
addresses two related but distinct issues: (1) The Food and Drug
Administration's (FDA) Unapproved Drugs Initiative (UDI) and (2) the
construction of the statutory exemptions from the definition of ``new
drugs'' subject to FDA approval under the federal Food, Drug, and
Cosmetic Act (FD&C Act), namely so-called pre-1938 grandfathered drugs
and drugs that are ``generally recognized as safe and effective'' or
``GRASE.''

I. Unapproved Drugs Initiative

    In 1938, Congress created the modern scheme for federal regulation
of drugs. Before 1938, there was no requirement under federal law for a
manufacturer to obtain FDA approval before marketing a drug. Today, as
a general rule, under the FD&C Act, a ``new drug'' must be approved by
the FDA for safety and efficacy pursuant to an approved New Drug
Application (NDA) or Abbreviated New Drug Application (ANDA) before the
drug is introduced into interstate commerce. See FD&C Act 201(p), 21
U.S.C. 321(p) (defining ``new drug'' under the Act); FD&C Act 505(a),
21 U.S.C. 355(a) (``No person shall introduce or deliver for
introduction into interstate commerce any new drug, unless an approval
of an application . . . is effective with respect to such drug.''). A
``person'' that introduces a ``new drug'' into interstate commerce is
subject to, among other sanctions, injunctions and/or having the
subject product seized in an ex parte proceeding under admiralty rules.
See FD&C Act 302, 21 U.S.C. 332 (injunction authority); FD&C Act 304,
21 U.S.C. 334 (seizure authority).
    Not all drugs are ``new drugs'' which require FDA approval. There
are two primary carve-outs from the FD&C Act's definition of ``new
drug.'' \1\ First, when Congress enacted the modern FD&C Act in 1938,
it exempted from the definition of ``new drug'' all drugs ``subject to
the Food and Drugs Act of June 30, 1906, as amended, and if at such
time its labeling contained the same representations concerning the
conditions of its use.'' FD&C Act 201(p)(1), 21 U.S.C. 321(p)(1).
Second, drugs that are generally recognized as safe and effective which
have also ``been used to a material extent or for a material time'' are
not ``new drugs.'' FD&C Act 201(p)(1) and (2), 21 U.S.C. 321(p)(1) and
(2). Drugs that meet either of these exceptions may be legally marketed
without FDA pre-approval for safety and efficacy, subject to the
agency's other regulatory authorities.
---------------------------------------------------------------------------

    \1\ There is a third, related exemption which relieves
manufacturers from the obligation of showing their drugs are
effective prior to marketing. In section 107(c)(4) of the Drug
Amendments of 1962, Public Law 87-81, 76 Stat. 780, 789 (Oct. 10,
1962), Congress exempted from the efficacy requirement ``product[s]
that, on the day before the 1962 amendments became effective, (A)
[were] used or sold commercially in the United States, (B) [were]
generally recognized by the experts as safe; and (C) [were] not
`covered' by an `effective' application.'' USV Pharmaceutical Corp.
v. Weinberger, 412 U.S. 655, 653 (1973). In Weinberger, the Supreme
Court held that so-called ``me-too drugs,'' i.e., drugs that were
copies of NDA drugs, were effectively ``covered'' by an effective
application and thus subject to the efficacy requirement just like
drugs covered by NDAs. Id. at 664-65. Practically, Weinberger left
as the lone remaining candidates for this exemption from the
efficacy requirement drugs (a) on the market prior to 1962, (b)
generally recognized as safe, and (c) not themselves subject to a
1938-1962 ``effective'' NDA.
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    Through a guidance document issued in 2006 and later revised in
2011, and without conducting notice-and-comment rulemaking, FDA
launched a program called the Unapproved Drugs Initiative (UDI).\2\ The
UDI sprang from a laudable objective, namely to reduce the number of
unapproved drugs on the market. To achieve this end, FDA provided in
its 2011 UDI Guidance that ``the first company to obtain an approval
[of a previously unapproved drug] will have a period of de facto market
exclusivity before other products obtain approval.'' \3\ The agency
``hope[d] that this period of market exclusivity will provide an
incentive to firms to be the first to obtain approval to market a
previously unapproved drug.'' \4\ Ultimately, manufacturers of older
drugs previously thought to be exempt from the FDA approval requirement
obtained market exclusivity for those products after FDA took
unapproved versions off the market. An unintended consequence of the
``period of de facto market exclusivity'' provided by the UDI allowed
manufacturers an opportunity to raise prices in an environment largely
insulated from market competition.
---------------------------------------------------------------------------

    \2\ FDA, Marketed Unapproved Drugs--Compliance Policy Guide Sec.
440.100, Marketed New Drugs Without Approved NDAs or ANDAs (June
2006) (hereinafter the 2006 Guidance); FDA, Marketed Unapproved
Drugs--Compliance Policy Guide Sec. 440.100, Marketed New Drugs
Without Approved NDAs or ANDAs (Sept. 19, 2011) (hereinafter the
2011 Guidance).
    \3\ 2011 Guidance at 8.
    \4\ Id.
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    Based on its ongoing review of FDA regulatory programs, the
Department has decided to withdraw the 2006 and 2011 Guidance,
effective thirty days after the date of publication of this Notice in
the Federal Register. All compliance manuals, website statements, and
other informal issuances with respect to the 2006 and 2011 Guidance are
also hereby withdrawn. The withdrawal of the 2006 and 2011 Guidance
Documents complies with FDA's current Good Guidance Practices
regulation, which allows for ``periodic[ ] review of [of] existing
guidance documents to determine whether they need to be changed or
withdrawn.'' 21 CFR 10.115(k)(1). Nothing in this Notice otherwise
limits FDA's authority to take action against manufacturers of
unapproved drugs that meet the statutory definition of a ``new drug''
(such as, for example, an unapproved drug that claims to mitigate,
treat, or cure COVID-19) or violate the FD&C Act in other ways.
Further, nothing in this Notice limits FDA's grant of regulatory
exclusivities authorized by statute, such as a new chemical entity
exclusivity, orphan drug exclusivity, or pediatric exclusivity. This
Notice does not apply to drugs subject to (1) Investigational New Drug
applications (IND) that are in effect as of the effective date of this
Notice, (2) any subsequent NDA based on new clinical trial
investigations (other than bioavailability studies) derived under such
IND, and (3) existing approved NDAs.
    The Department is withdrawing the 2006 and 2011 Guidances for
several evidence-based reasons. After the UDI began, reports emerged
that Americans were paying significantly more for prescription drugs
approved by FDA through the UDI than they had paid previously. One
report noted that a drug approved through the UDI ``sells for about
$4.50 a tablet--nearly 50 times the price of the unapproved version.''
\5\ Another report asserted that ``[t]hanks at least partially to the
FDA program, the price of vasopressin . . . has risen 10-fold'' and the
cost of ``a vial of

neostigimine . . . has gone from less than $5 to $90.'' \6\
---------------------------------------------------------------------------

    \5\ Harris Meyer, The High Price of FDA Approval, Kaiser Health
News, Dec. 29, 2009, https://khn.org/news/fda-approval/.
    \6\ Michael Hiltzik, The little-known FDA program that's driving
drug prices higher, L.A. Times (Sept. 23, 2015), https://www.latimes.com/business/hiltzik/la-fi-mh-the-little-known-fda-program-20150923-column.html.
---------------------------------------------------------------------------

    In 2017, scholars from the Yale School of Medicine and the
University of Utah published a peer-reviewed study corroborating the
previous reports.\7\ The study reviewed 34 drugs subject to the UDI
between 2006 and 2015. The scholars found the average wholesale unit
price of 26 of the 34 drugs for which pricing data was available
increased by a median of 37% (interquartile range of 23%-204%).\8\ The
average wholesale unit price of 11 of the drugs surveyed in the study
increased by more than 128%.\9\
---------------------------------------------------------------------------

    \7\ Ravi Gupta et al., The FDA Unapproved Drugs Initiative: An
Observational Study of the Consequences for Drug Prices and
Shortages in the United States, 23 J. of Man. Care & Specialty
Pharm. 1066 (Oct. 2017).
    \8\ Id. at 1071.
    \9\ See id. at 1072.
---------------------------------------------------------------------------

    The study also linked the UDI to drug shortages, which the authors
defined as ``a supply issue that affects how a pharmacy prepares or
dispenses a drug product that influences patient care when prescribers
must use an alternative agent.'' \10\ In this regard, the scholars
found that 24 of the 34 drugs experienced shortages after FDA took
enforcement action after an entity obtained FDA approval of a
previously unapproved drug. The median shortage was 217 days.\11\
---------------------------------------------------------------------------

    \10\ Id. at 1068.
    \11\ Id. at 1073.
---------------------------------------------------------------------------

    Finally, the authors considered whether the UDI generated new
clinical data evidence for older drugs. The authors found that, of the
nineteen drugs that obtained FDA approval during the study period, only
two were supported by ``new clinical trial evidence.'' \12\ The other
seventeen drugs ``were supported by literature reviews and
bioequivalence to older drug products.'' \13\
---------------------------------------------------------------------------

    \12\ Id.
    \13\ Id.; see also Aaron S. Kesselheim and Daniel H. Solomon,
Incentives for Drug Development--The Curious Case of Colchicine, N.
Engl. J. Med. 362;22 at 2046 (noting the dramatic rise in the price
of Colchicine after implementation of the UDI, but that ``there is
no evidence of any meaningful improvement to the public health''
from the regulatory changes).
    \13\ 36 FR 14662, 14662-63 (Aug. 7, 1971).
---------------------------------------------------------------------------

    Therefore, the Department has concluded that while the UDI began
with laudable goals, it has had numerous negative, unintended
consequences on Americans' access to prescription drugs and generated
very limited benefits.
    Moreover, the fact that the program was initiated through guidance,
as opposed to notice-and-comment rulemaking, further supports the
Department's decision to withdraw the 2006 and 2011 Guidances, because
the Department has serious legal concerns about whether the UDI was
implemented through legally permissible procedures.\14\ The Department
recognizes that some persons might contend that they have reliance
interests in the 2011 Guidance remaining in effect. In Dep't of
Homeland Sec. v. Regents of the Univ. of California, 140 S. Ct. 1891
(2020), the Supreme Court struck down the Department of Homeland
Security's rescission of the Deferred Action for Childhood Arrivals
(DACA) immigration program, in part based on the reliance interests of
persons eligible to obtain the benefits of the program. Notably, in
that case, immigration authorities ``solicited applications from
eligible aliens, instituted a standardized review process, and sent
formal notices indicating whether the alien would receive the two-year
forbearance.'' Id. As the Court explained, DACA ``created a program for
conferring affirmative immigration relief.'' Id.
---------------------------------------------------------------------------

    \14\ See, e.g., 5 U.S.C. 553. The Department also has concerns
regarding whether the issuance of the 2011 Guidance complied with
FDA's good guidance practices regulation, 21 CFR 10.115, in effect
at the time. FDA issued the 2011 Guidance ``without public comment
because the Agency has determined that prior public participation is
not feasible or appropriate.'' 76 FR 58398 (Sept. 21, 2011).
---------------------------------------------------------------------------

    The UDI is distinguishable from the DACA program. Unlike DACA, the
2011 Guidance described how the FDA intended to exercise its
enforcement discretion, but stopped short of committing FDA to any
particular action. FDA stated that it was ``more likely to take
enforcement action'' against unapproved competitors of newly approved
drugs under the UDI, but that the agency ``intend[s] to take into
account the circumstances once the product is approved in determining
how to exercise our enforcement discretion with regard to the
unapproved products.'' \15\ Moreover, the 2011 Guidance stated that it
``does not create or confer any rights for or on any person and does
not operate to bind FDA or the public.'' \16\ Any reliance interests
are thus illusory. Furthermore, Congress vested FDA with the sole
authority to enforce the FD&C Act. FD&C Act 310, 21 U.S.C. 337. Under
Heckler v. Chaney, 470 U.S. 821 (1985), FDA's decision about the extent
to which it shall enforce the FD&C Act is unreviewable under the
Administrative Procedure Act.
---------------------------------------------------------------------------

    \15\ 2011 Guidance at 7.
    \16\ Id. at 2.
---------------------------------------------------------------------------

    Even if there were cognizable reliance interests in the UDI, the
Department has ample evidence-based justification for rescinding the
2006 and 2011 Guidances. After more than fourteen years of experience
with the program, evidence has emerged that the UDI has caused
significant prescription drug price increases and drug shortages while
providing limited new clinical data on older drugs. The Department
believes these costs imposed on American patients and taxpayers
outweigh any reliance interests that may exist in the program. The
Department has also considered the public health effects of withdrawing
the 2006 and 2011 Guidances. As the 2011 Guidance acknowledges, there
are ``several thousand'' products on the market that lack FDA
approval.\17\ To the extent this program has limited patient access to
important, safe medications due to price increases or drug shortages,
the withdrawal of the 2006 and 2011 Guidances will have a positive
impact on public health. Moreover, eliminating this program allows
FDA's resources to be directed toward monitoring unapproved ``new
drugs'' that fall squarely within the traditional scope of the
definition of that term in the FD&C Act. At the same time, the Notice
allows FDA to use its limited review resources on innovative potential
therapies, as opposed to older drugs with longstanding use.
---------------------------------------------------------------------------

    \17\ Id. at 3.
---------------------------------------------------------------------------

    Besides, any reliance interests (if they existed) would be minimal.
This Notice does not apply to drugs subject to (1) INDs in effect as of
the effective date of this Notice, (2) any subsequent NDA based on new
clinical investigations (other than bioavailability studies) derived
under such IND, and (3) existing approved NDAs.

II. Pre-1938 Grandfathered and GRASE Drugs; Request for Information

    As noted above, when Congress enacted the FD&C Act in 1938 and
later amended the Act in 1962, it exempted certain drugs from the FDA
approval requirement. Section 201(p) of the FD&C Act, 21 U.S.C. 321(p),
excludes from the definition of ``new drug'' certain drugs marketed
prior to June 25, 1938 and drugs generally recognized as safe and
effective, or GRASE. In the 2011 Guidance, FDA stated that ``it is not
likely that any currently marketed prescription drug is grandfathered
or is otherwise not a new drug,'' though the

agency stated ``that it is at least theoretically possible.'' \18\
---------------------------------------------------------------------------

    \18\ Id. at 12 (emphasis in original).
---------------------------------------------------------------------------

    That was not always the case. For many years, FDA acknowledged that
at least some drugs are not ``new drugs'' subject to FDA approval prior
to marketing. In a 1980 version of the Orange Book, FDA stated that
``[t]he law also permits drugs to be legally marketed without such
fully approved applications under certain circumstances,'' including
``drugs marketed prior to 1938 that are not subject to the pre-market
clearance procedures of the law'' and ``drug products marketed between
1938 and 1962 that were approved for safety but not effectiveness.''
\19\ In the same publication, the agency went on to identify specific
products, noting ``commonly used large volume intravenous products are
not included on the List [of FDA-approved drugs] (e.g., dextrose 5%
with water, dextrose 10% with water, sodium chloride 0.9% injection),''
since ``all of these drug products came on the market in glass
containers before 1938 and have not been required to obtain an approved
new drug application as a condition of marketing.'' \20\ In the 2000
edition of the Orange Book, FDA cited to the barbiturate
``Phenobarbital Tablets'' as an example of ``pre-1938 drugs.'' \21\ The
2011 Guidance, issued absent notice-and-comment rulemaking and without
prior public comment, contains no acknowledgement of these prior
positions.\22\
---------------------------------------------------------------------------

    \19\ FDA, Approved Prescription Drug Products with Therapeutic
Equivalence Evaluations (herein the Orange Book), at I-3 (1st ed.
1980).
    \20\ Id. at I-13.
    \21\ Id. at I-13. FDA, Orange Book, at v (2000); see also FDA,
Orange Book, at iv (29th ed. 2009) (containing same reference to
``pre-1938 drugs'' and phenobarbital tablets). FDA included a
reference to ``pre-1938 drugs'' like phenobarbital tablets in the
Orange Book as late as 2016, FDA, Orange Book, at iv (36th ed.
2016), but removed the reference in its 2017 edition and subsequent
versions.
    \22\ Cf. F.C.C. v. Fox Television Stations, Inc., 556 U.S. 502,
515 (2009) (``To be sure, the requirement that an agency provide
reasoned explanation for its action would ordinarily demand that it
display awareness that it is changing position.'')
---------------------------------------------------------------------------

    This evolution in the agency's thinking has had consequences. Under
the UDI, FDA required the manufacturer of an epinephrine brand which
originally came onto the market in 1901 to submit an NDA.\23\ The drug
colchicine, a product FDA acknowledged ``was available in oral dosage
form during the 19th century,'' \24\ was also approved through the UDI.
The interpretation of the definition of ``new drug'' espoused in the
2011 Guidance essentially foreclosed the possibility that these two
century-old drugs were pre-1938 grandfathered drugs exempt from the
approval process. The 2017 study discussed above found that the average
wholesale unit price of epinephrine and colchicine increased by 58.3%
and 3,323.5%, respectively,\25\ costs absorbed by American patients and
taxpayers.
---------------------------------------------------------------------------

    \23\ FDA, Ctr. For Drug Evaluation and Research, Application
Number: 204200Origs1s000, 204200Orig2s000, Summary Review, at 3,
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/204200Orig1Orig2s000SumR.pdf.
    \24\ 75 FR 60768 (Oct. 1, 2010).
    \25\ Gupta, supra note 7, at 1072; see also Aaron S. Kesselheim
and Daniel H. Solomon, Incentives for Drug Development--The Curious
Case of Colchicine, N. Engl. J. Med. 362;22 at 2046 (noting the
dramatic rise in the price of Colchicine after implementation of the
UDI, but that ``there is no evidence of any meaningful improvement
to the public health'' from the regulatory changes).
---------------------------------------------------------------------------

    The regulatory history of the prescription drug Daraprim raises
similar issues. FDA originally approved Daraprim (pyrimethamine) for
safety in 1953, and later deemed the drug effective through the Drug
Efficacy Study Implementation, or DESI review process.\26\ The drug is
listed on the World Health Organization's List of Essential
Medications, ``a list of minimum medicine needs for a basic health-care
system, listing the most efficacious, safe and cost-effective medicines
for priority conditions.'' \27\ In 2015, the company Turing
Pharmaceuticals ``raised the price [of the drug] to $750 a tablet from
$13.50, bringing the annual cost of treatment for some patients to
hundreds of thousands of dollars.'' \28\ Turing came by this windfall,
at least in part, because of FDA's interpretation of the definition of
``new drug'' in the FD&C Act as articulated in the 2006 and 2011
Guidances, a view that foreclosed the possibility that Daraprim, a drug
more than sixty years old, could ever qualify as GRASE. That position
effectively prevented other manufacturers of generic versions of this
product from entering the market without an approved abbreviated new
drug application, allowing Turing to enjoy a single-source position in
the marketplace while potential competitors went through the regulatory
process. In February 2016, Congress held a hearing on this widely-
publicized issue. Ultimately, FDA approved a generic competitor for
this single-source drug in February 2020.
---------------------------------------------------------------------------

    \26\ 36 FR 14662, 14662-63 (Aug. 7, 1971).
    \27\ World Health Organization, 20th WHO Model List of Essential
Medications, at 24 (Mar. 2017).
    \28\ Andrew Pollack, Drug Goes From $13.50 a Tablet to $750,
Overnight, N.Y. Times, Sept. 20, 2015, https://www.nytimes.com/2015/09/21/business/a-huge-overnight-increase-in-a-drugs-price-raises-protests.html.
---------------------------------------------------------------------------

    The Department wishes to engage with the public on the contours of
the exceptions to the definition of ``new drug.'' In this regard, HHS
is reviewing whether certain drugs, including the drug subject to
Congressional scrutiny in 2016, might qualify as exempt from the FDA
approval requirement. To aid that effort, HHS asks for input from
patients, health care providers, industry, and other stakeholders to
provide information responsive to any of the topics below:
    1. Lists of drugs marketed prior to June 25, 1938 that are
currently available on the market.
    2. The extent to which drugs marketed prior to June 25, 1938, or
drugs that might qualify as GRASE, have regulatory approvals in
countries outside the United States.
    3. Whether there would be adverse clinical or economic consequences
to deeming as GRASE those drugs previously approved by the FDA for
which patent and regulatory exclusivity have expired.
    4. Any published literature reviews or clinical studies related to
any drugs potentially exempt from the new drug approval requirement.

    Dated: November 20, 2020.
Alex M. Azar II,
Secretary, Department of Health and Human Services.
[FR Doc. 2020-26133 Filed 11-24-20; 8:45 am]
BILLING CODE 4150-26-P


[Federal Register: February 13, 2008 (Volume 73, Number 30)]
[Notices]
[Page 8400-8402]
[DOCID:fr13fe08-170]

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DEPARTMENT OF TRANSPORTATION

Pipeline and Hazardous Materials Safety Administration

[Docket No. PHMSA-2008-0018 (Notice No. 08-1)]

Information Collection Activities Under OMB Review; 2008 Renewals

AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA),
DOT.

ACTION: Notice and request for comments.

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

SUMMARY: In compliance with the Paperwork Reduction Act of 1995, this
notice announces that the Information Collection Requests (ICR)
abstracted below will be forwarded to the Office of Management and
Budget (OMB) for review and comments. The ICRs describe the nature of
the information collections and their expected burden. A Federal
Register Notice with a 60-day comment period soliciting comments on the
following collections of information was published in the Federal
Register on November 30, 2007 [72 FR 67782] under Docket No. PHMS-2007-
27181 (Notice No. 07-11). No comments pertaining to the renewal of
these information collections were received.

DATES: Interested persons are invited to submit comments on or before
March 14, 2008.

ADDRESSES: Send comments regarding the burden estimate, including
suggestions for reducing the burden, to the Office of Management and
Budget (OMB), Attention: Desk Officer for PHMSA, 725 17th Street, NW.,
Washington, DC 20503. Comments are invited on: Whether the proposed
collection of information is necessary for the proper performance of
the functions of the Department, including whether the information will
have practical utility; the accuracy of the Department's estimate of
the burden of the proposed information collection; ways to enhance the
quality, utility and clarity of the information to be collected; and
ways to minimize the burden of the collection of information on
respondents, including the use of automated collection techniques or
other forms of information technology. A comment to OMB is most
effective if OMB receives it within 30 days of publication.

FOR FURTHER INFORMATION CONTACT: Deborah Boothe or T. Glenn Foster,
U.S. Department of Transportation, Office of Hazardous Materials
Standards (PHH-11), Pipeline and Hazardous Materials Safety
Administration, 1200 New Jersey Avenue, SE., East Building, 2nd Floor,
Washington, DC 20590-0001, Telephone<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION: Section 1320.8(d), Title 5, Code of Federal
Regulations requires PHMSA to provide interested members of the public
and affected agencies an opportunity to comment on information
collection and recordkeeping requests. This notice identifies
information collection requests that PHMSA will be submitting to OMB
for renewal and extension. These information collections are contained
in 49 CFR parts 110 and 130 and the Hazardous Materials Regulations
(HMR; 49 CFR parts 171-180). PHMSA has revised burden estimates, where
appropriate, to reflect current reporting levels or adjustments based
on changes in proposed or final rules published since the information
collections were last approved. The following information is provided
for each information collection: (1) Title of the information
collection, including former title if a change is being made; (2) OMB
control number; (3) abstract of the information collection activity;
(4) description of affected public; (5) estimate of total annual
reporting and recordkeeping burden; and (6) frequency of collection.
PHMSA will request a three-year term of approval for each information
collection activity and, when approved by OMB, publish notice of the
approval in the Federal Register.
    PHMSA requests comments on the following information collections:
    Title: Testing, Inspection and Marking Requirements for Cylinders.
    OMB Control Number: 2137-0022.
    Type of Request: Extension of a currently approved information
collection.
    Abstract: Requirements in Sec.  173.301 for qualification,
maintenance and use of cylinders require that cylinders be periodically
inspected and retested to ensure continuing compliance with packaging
standards. Information collection requirements address registration of
retesters and marking of cylinders by retesters with their
identification number and retest date following conduct of tests.
Records showing the results of inspections and retests must be kept by
the cylinder owner or designated agent until expiration of the retest
period or until the cylinder is reinspected or retested, whichever
occurs first. These requirements are intended to ensure that retesters
have the qualifications to perform tests and to identify to cylinder
fillers and users that cylinders are qualified for continuing use.
Information collection requirements in Sec.  173.303 require that
fillers of acetylene cylinders keep, for at least 30 days, a daily
record of the representative pressure to which cylinders are filled.
    Affected Public: Fillers, owners, users and retesters of reusable
cylinders.
    Recordkeeping:
    Estimated Number of Respondents: 139,352.
    Estimated Number of Responses: 153,287.
    Estimated Annual Burden Hours: 168,431.
    Frequency of collection: On occasion.

    Title: Approvals for Hazardous Materials.
    OMB Control Number: 2137-0557.
    Type of Request: Extension of a currently approved information
collection.
    Abstract: Without these requirements there is no means to: (1)
Determine whether applicants who apply to become designated approval
agencies are qualified to evaluate package design, test packages,
classify hazardous materials, etc.; (2) verify that various containers
and special loading requirements for vessels meet the requirements of
the HMR; and (3) assure that regulated hazardous materials pose no
danger to life and property during transportation.
    Affected Public: Businesses and other entities which must meet the
approval requirements in the HMR.
    Recordkeeping:
    Estimated Number of Respondents: 10,723.
    Estimated Number of Responses: 11,074.
    Estimated Annual Burden Hours: 25,605.
    Frequency of collection: On occasion.

    Title: Rail Carrier and Tank Car Tank Requirements.
    OMB Control Number: 2137-0559.
    Type of Request: Extension of a currently approved information
collection.
    Abstract: This information collection consolidates and describes
the information provisions in parts 172, 173, 174, 179, and 180 of the
HMR on the transportation of hazardous materials by rail and the
manufacture, qualification, maintenance and use of tank cars. The types
of information collected include:
    (1) Approvals of the Association of American Railroads (AAR) Tank
Car

Committee: An approval is required from the AAR Tank Car Committee for
a tank car to be used for a commodity other than those specified in
part 173 and on the certificate of construction. This information is
used to ascertain whether a commodity is suitable for transportation in
a tank car. AAR approval also is required for an application for
approval of designs, materials and construction, conversion or
alteration of tank car tanks constructed to a specification in part 179
or an application for construction of tank cars to any new
specification. This information is used to ensure that the design,
construction or modification of a tank car or the construction of a
tank car to a new specification is performed in accordance with the
applicable requirements.
    (2) Progress Reports: Each owner of a tank car that is required to
be modified to meet certain requirements specified in Sec.  173.31(b)
must submit a progress report to the Federal Railroad Administration
(FRA). This information is used by FRA to ensure that all affected tank
cars are modified before the regulatory compliance date.
    (3) FRA Approvals: An approval is required from FRA to transport a
bulk packaging (such as a portable tank, IM portable tank, intermediate
bulk container, cargo tank, or multi-unit tank car tank) containing a
hazardous material in container-on-flat-car or trailer-on-flat-car
service other than as authorized by Sec.  174.63. FRA uses this
information to ensure that the bulk package is properly secured using
an adequate restraint system during transportation. Also an FRA
approval is required for the movement of any tank car that does not
conform to the applicable requirements in the HMR. PHMSA proposed
(September 30, 1999; 64 FR 53169) to broaden this provision to include
the movement of covered hopper cars, gondola cars, and other types of
railroad equipment when they no longer conform to Federal law but may
safely be moved to a repair location. These latter movements are
currently being reported under the information collection for special
permit applications.
    (4) Manufacturer Reports and Certificate of Construction: These
documents are prepared by tank car manufacturers and are used by
owners, users and FRA personnel to verify that rail tank cars conform
to the applicable specification.
    (5) Quality Assurance Program: Facilities that build, repair, and
ensure the structural integrity of tank cars are required to develop
and implement a quality assurance program. This information is used by
the facility and DOT compliance personnel to ensure that each tank car
is constructed or repaired in accordance with the applicable
requirements.
    (6) Inspection Reports: A written report must be prepared and
retained for each tank car that is inspected and tested in accordance
with Sec.  180.509 of the HMR. Rail carriers, users, and the FRA use
this information to ensure that rail tank cars are properly maintained
and in safe condition for transporting hazardous materials.
    Affected Public: Manufacturers, owners and rail carriers of tank
cars.
    Recordkeeping:
    Estimated Number of Respondents: 266.
    Estimated Number of Responses: 16,782.
    Estimated Annual Burden Hours: 2,689.
    Frequency of collection: Annually.

    Title: Inspection and Testing of Meter Provers.
    OMB Control Number: 2137-0620.
    Type of Request: Extension of a currently approved information
collection.
    Abstract: This information collection and recordkeeping burden is
the result of efforts to eliminate special permits that are no longer
needed and incorporate the use, inspection, and maintenance of
mechanical displacement meter provers (meter provers) used to check the
accurate flow of liquid hazardous materials into bulk packagings, such
as portable tanks and cargo tank motor vehicles, under the HMR. These
meter provers are used to ensure that the proper amount of liquid
hazardous materials is being loaded and unloaded involving bulk
packagings, such as cargo tanks and portable tanks. These meter provers
consist of a gauge and several pipes that always contain small amounts
of the liquid hazardous material in the pipes as residual material;
and, therefore, must be inspected and maintained in accordance with the
HMR to ensure they are in proper calibration and working order. These
meter provers are not subject to the specification testing and
inspection requirements in Part 178. However, these meter provers must
be visually inspected annually and hydrostatic pressure tested every
five years in order to ensure they are properly working as specified in
Sec.  173.5a of the HMR. Therefore, this information collection
requires that:
    (1) Each meter prover must undergo and pass an external visual
inspection annually to ensure that the meter provers used in the flow
of liquid hazardous materials into bulk packagings are accurate and in
conformance with the performance standards in the HMR.
    (2) Each meter prover must undergo and pass a hydrostatic pressure
test at least every five years to ensure that the meter provers used in
the flow of liqiuid hazardous materials into bulk packagings are
accurate and in conformance with the performance standards in the HMR.
    (3) Each meter prover successfully completing the test and
inspection must be marked in accordance with Sec.  180.415(b) and in
accordance with Sec.  173.5a.
    (4) Each owner must retain a record of the most recent visual
inspection and pressure test until the meter prover is requalified.
    Affected Public: Owners of meter provers used to measure liquid
hazardous materials flow into bulk packagings such as cargo tanks and
portable tanks.
    Recordkeeping:
    Estimated Number of Respondents: 50.
    Estimated Number of Responses: 250.
    Estimated Annual Burden Hours: 175.
    Frequency of collection: On occasion.

    Title: Requirements for United Nations (UN) Cylinders.
    OMB Control Number: 2137-0621.
    Type of Request: Extension of a currently approved information
collection.
    Abstract: This information collection and recordkeeping burden is
the result of efforts to amend the HMR to adopt standards for the
design, construction, maintenance and use of cylinders and multiple-
element gas containers (MEGCs) based on the standards contained in the
United Nations (UN) Recommendations on the Transport of Dangerous
Goods. Aligning the HMR with the UN Recommendations will promote
flexibility, permit the use of technological advances for the
manufacture of the pressure receptacles, provide for a broader
selection of pressure receptacles, reduce the need for exemptions, and
facilitate international commerce in the transportation of compressed
gases. Information collection requirements address domestic and
international manufacturers of cylinders that request approval by the
approval agency for cylinder design types. The approval process for
each cylinder design type includes review, filing, and recordkeeping of
the approval application. The approval agency is required to maintain a
set of the approved drawings and calculations for

each design it reviews and a copy of each initial design type approval
certificate approved by the Associate Administrator for not less than
20 years.
    Affected Public: Fillers, owners, users, and retesters of UN
cylinders.
    Recordkeeping:
    Estimated Number of Respondents: 50.
    Estimated Number of Responses: 150.
    Estimated Annual Burden Hours: 900.
    Frequency of collection: On occasion.

    Issued in Washington, DC on February 8, 2008.
Edward T. Mazzullo,
Director, Office of Hazardous Materials Standards.
 [FR Doc. E8-2662 Filed 2-12-08; 8:45 am]

BILLING CODE 4910-60-P