[Federal Register Volume 88, Number 83 (Monday, May 1, 2023)]
[Notices]
[Pages 26562-26563]
[FR Doc No: 2023-09179]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2021-D-0875]

S12 Nonclinical Biodistribution Considerations for Gene Therapy
Products; International Council for Harmonisation; Guidance for
Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``S12
Nonclinical Biodistribution Considerations for Gene Therapy Products.''
The guidance was prepared under the auspices of the International
Council for Harmonisation of Technical Requirements for Pharmaceuticals
for Human Use (ICH). The final guidance provides harmonized
recommendations for the conduct and overall design of nonclinical
biodistribution (BD) studies for gene therapy (GT) products. The
recommendations in the guidance endeavor to facilitate the development
of investigational GT products, while avoiding unnecessary use of
animals, in accordance with the 3Rs (reduce/refine/replace) principles.
The final guidance replaces the draft guidance entitled ``S12
Nonclinical Biodistribution Considerations for Gene Therapy Products''
issued on September 9, 2021.

DATES: The announcement of the guidance is published in the Federal
Register on May 1, 2023.

ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked, and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2021-D-0875 for ``S12 Nonclinical Biodistribution Considerations
for Gene Therapy Products.'' Received comments will be placed in the
docket and, except for those submitted as ``Confidential Submissions,''
publicly viewable at https://www.regulations.gov or at the Dockets
Management Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-
402-7500.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For

more information about FDA's posting of comments to public dockets, see
80 FR 56469, September 18, 2015, or access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852,<PHONE_NUMBER>.
    You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
    Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002, or the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send
one self-addressed adhesive label to assist that office in processing
your requests. The guidance may also be obtained by mail by calling
CBER at 1-800-835-4709 or<PHONE_NUMBER>. See the SUPPLEMENTARY
INFORMATION section for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Alyssa Galaro, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 6260, Silver Spring, MD, 20993-0002, 301-
796-6589.
    Regarding the ICH: Jill Adleberg, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6364, Silver Spring, MD 20993-0002,<PHONE_NUMBER>,
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry
entitled ``S12 Nonclinical Biodistribution Considerations for Gene
Therapy Products.'' The guidance was prepared under the auspices of
ICH. ICH has the mission of achieving greater regulatory harmonization
worldwide to ensure that safe, effective, high-quality medicines are
developed, registered, and maintained in the most resource-efficient
manner.
    By harmonizing the regulatory requirements in regions around the
world, ICH guidelines enhance global drug development, improve
manufacturing standards, and increase the availability of medications.
For example, ICH guidelines have substantially reduced duplicative
clinical studies, prevented unnecessary animal studies, standardized
the reporting of important safety information, and standardized
marketing application submissions.
    The six Founding Members of the ICH are FDA; the Pharmaceutical
Research and Manufacturers of America; the European Commission; the
European Federation of Pharmaceutical Industries Associations; the
Japanese Ministry of Health, Labour, and Welfare; and the Japanese
Pharmaceutical Manufacturers Association. The Standing Members of the
ICH Association include Health Canada and Swissmedic. ICH membership
continues to expand to include other regulatory authorities and
industry associations from around the world (refer to https://www.ich.org/).
    ICH works by engaging global regulatory and industry experts in a
detailed, science-based, and consensus-driven process that results in
the development of ICH guidelines. The regulators around the world are
committed to consistently adopting these consensus-based guidelines,
realizing the benefits for patients and for industry.
    As a Founding Regulatory Member of ICH, FDA plays a major role in
the development of each of the ICH guidelines, which FDA then adopts
and issues as guidance for industry. FDA's guidance documents do not
establish legally enforceable responsibilities. Instead, they describe
the Agency's current thinking on a topic and should be viewed only as
recommendations, unless specific regulatory or statutory requirements
are cited.
    In the Federal Register of September 9, 2021 (86 FR 50536), FDA
published a notice announcing the availability of a draft guidance
entitled ``S12 Nonclinical Biodistribution Considerations for Gene
Therapy Products.'' The notice gave interested persons an opportunity
to submit comments by November 8, 2021.
    After consideration of the comments received and revisions to the
guideline, a final draft of the guideline was submitted to the ICH
Assembly and endorsed by the regulatory agencies on March 14, 2023.
    This guidance finalizes the draft guidance of the same title issued
on September 9, 2021. The guidance is intended to promote harmonization
of recommendations for the BD assessment for investigational GT
products and facilitate a more efficient and timely nonclinical
development program. The revisions to the draft guidance aimed to
clarify key elements of the BD assessment by providing additional
information on selecting dose levels and identifying a biologically
relevant model. Additional details were provided on what product and
study characteristics should be considered to determine if previous BD
data can be leveraged.
    This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``S12 Nonclinical Biodistribution
Considerations for Gene Therapy Products.'' It does not establish any
rights for any person and is not binding on FDA or the public. You can
use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This guidance contains no collection of information. Therefore,
clearance by the Office of Management and Budget under the Paperwork
Reduction Act of 1995 is not required.

III. Electronic Access

    Persons with access to the internet may obtain the final guidance
at https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

    Dated: April 26, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-09179 Filed 4-28-23; 8:45 am]
BILLING CODE 4164-01-P


[Federal Register Volume 78, Number 204 (Tuesday, October 22, 2013)]
[Notices]
[Pages 62614-62615]
[FR Doc No: 2013-24530]

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DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. EL14-4-000]

CalWind Resources, Inc. v. California Independent System Operator
Corporation; Notice of Complaint

    Take notice that on October 11, 2013, pursuant to section 206 of
the Federal Power Act (FPA), 16 U.S.C. 824e and Rule 206 of the Federal
Energy Regulatory Commission's (Commission) Rules of Practice and
Procedure, 18 CFR 385.206 (2013), CalWind Resources, Inc. (Complainant)
filed a formal complaint against California Independent System Operator
Corporation (CAISO or Respondent), requesting that the Commission
direct CAISO to file an amendment to sections 25.1 and 25.1.2 of its
open access transmission tariff or, in the alternative, direct CAISO to
follow a tariff interpretation conforming to the Commission's policy,
as more fully described in the complaint.
    The Complainant certifies that copies of the complaint were served
on the contacts for the Respondent as listed on the Commission's list
of Corporate Officials.
    Any person desiring to intervene or to protest this filing must
file in

accordance with Rules 211 and 214 of the Commission's Rules of Practice
and Procedure (18 CFR 385.211, 385.214). Protests will be considered by
the Commission in determining the appropriate action to be taken, but
will not serve to make protestants parties to the proceeding. Any
person wishing to become a party must file a notice of intervention or
motion to intervene, as appropriate. The Respondent's answer and all
interventions, or protests must be filed on or before the comment date.
The Respondent's answer, motions to intervene, and protests must be
served on the Complainants.
    The Commission encourages electronic submission of protests and
interventions in lieu of paper using the ``eFiling'' link at http://www.ferc.gov. Persons unable to file electronically should submit an
original and 5 copies of the protest or intervention to the Federal
Energy Regulatory Commission, 888 First Street NE., Washington, DC
20426.
    This filing is accessible on-line at http://www.ferc.gov, using the
``eLibrary'' link and is available for review in the Commission's
Public Reference Room in Washington, DC. There is an ``eSubscription''
link on the Web site that enables subscribers to receive email
notification when a document is added to a subscribed docket(s). For
assistance with any FERC Online service, please email
<EMAIL_ADDRESS>or call<PHONE_NUMBER> (toll free). For
TTY, call<PHONE_NUMBER>.
    Comment Date: 5:00 p.m. Eastern Time on October 31, 2013.

    Dated: October 15, 2013.
Kimberly D. Bose,
Secretary.
[FR Doc. 2013-24530 Filed 10-21-13; 8:45 am]
BILLING CODE 6717-01-P


PAPERWORK REDUCTION ACT SUBMISSION Please read the instructions before completing this form. For additional forms or assistance in completing this form, contact your agency's Paperwork Clearance Officer. Send two copies of this form, the collection instrument to be reviewed, the Supporting Statement and any additional documentation to: Office of Information and Regulatory Affairs, Office of Management and Budget, Docket Library, Room 10102, 725 17th Street NW Washington, DC 20503.

1. Agency/ Subagency originating request EPA/ OSWER/ CEPPO 2. OMB control number b. G None a 2050  0172 3. Type of information collection ( check one) a. G New collection b. G Revision of a currently approved collection c. x Extension of a currently approved collection d. G Reinstatement, without change, of a previously approved collection for which approval has expired e. G Reinstatement, with change, of a previously approved collection for which approval has expired f. G Existing collection in use without an OMB control number 4. Type of review requested ( check one) a. x Regular b. G Emergency  Approval requested by: / / c. G Delegated 5. Small entities Will this information collection have a significant economic impact on a substantial number of small entities? Yes x No For b f, note item A2 of Supporting Statement Instructions 6. Requested expiration date a. x Three years from approval date b. G Other Specify: / /___

7. Title: Distribution of Off site Consequence Analysis Information under Section 112( r)( 7)( H) of the Clean Air Act ( CAA)

8. Agency form number( s) ( If applicable): 1981.02 9. Keywords: Chemical Safety Information, Site Security, Fuels Regulatory Relief Act, Off site consequence analysis, public access, risk management plan 10. Abstract: This information collection request ( ICR) supports the final rule, Accidental Release Prevention Requirements; Risk Management Programs Under the Clean Air Act Section 112( r)( 7); Distribution of Off Site Consequence Analysis Information, under CAA section 112( r) as amended by the Chemical Safety Information, Site Security, and Fuels Regulatory Relief Act ( P. L. 106 40). CAA section 112( r)( 7) required EPA to promulgate reasonable regulations and appropriate guidance to provide for the prevention and detection of accidental releases and for responses to such releases. The regulations include requirements for submittal of a risk management plan ( RMP) to EPA. The RMP includes information on offsite consequence analyses ( OCA) as well as other elements of the risk management program. EPA has made all RMP data except the OCA information available to the public on the Internet through a system called RMP* Info. The final rule will provide access to OCA information for governmental officials and the members of the public. This ICR includes the burden placed on the members of the public requesting OCA information ( providing personal identification and sign in at federal reading rooms). This ICR also includes burden on state and local officials deciding to obtain OCA information ( must submit a written request to EPA for OCA information and may provide reading rooms for the public to view OCA information for local facilities. ( Note: The ICR for the proposed rule was submitted under ICR 1656.08. To avoid confusion with the ICR already approved under OMB control no. 2050 0144 ( Risk Management Program Requirements and Petitions to Modify the List of Regulated Substances under Section 112( r) of the Clean Air Act), the ICR number for the final rule has been changed.)

11. Affected public ( Mark primary with " P" and all others that apply with " X") a. P Individuals or households d. Farms b. Business or other for profit e. X Federal Government c. Not for profit institutions f. P State, Local or Tribal Government 12. Obligation to respond ( Mark primary with " P" and all others that apply with " X") a. P Voluntary b. G Required to obtain or retain benefits c. G Mandatory 13. Annual reporting and recordkeeping hour burden a. Number of respondents 4,417 b. Total annual responses 4,417 1. Percentage of these responses collected electronically 0 % c. Total hours requested 15,840 d. Current OMB inventory 99,518 e. Difference  83,678 f. Explanation of difference 1. Program Change 0 2. Adjustment  83,678 14. Annual reporting and recordkeeping cost burden ( in thousands of dollars)

a. Total annualized capital/ startup costs 0 b. Total annual costs ( O& M) 1 c. Total annualized cost requested 1 d. Current OMB inventory 126 e. Difference  125 f. Explanation of difference 1. Program change 0 2. Adjustment  125 15. Purpose of information collection ( Mark Primary With " P" and all others that apply with " X") a. __ Application for benefits e. __ Program planning or management b. __ Program evaluation f. __ Research c. __ General purpose statistics g. P Regulatory or compliance d. __ Audit 16. Frequency of recordkeeping or reporting ( check all that apply) a. x Recordkeeping b. Q Third party disclosure c. x Reporting 1. X On occasion 2. Q Weekly 3. Q Monthly 4. Q Quarterly 5. Q Semi annually 6. Q Annually 7. Q Biannually 8. Q Other ( describe)

17. Statistical methods Does this information collection employ statistical methods?

Q Yes X No 18. Agency contact ( person who can best answer questions regarding the content of this submission) Name: Sicy Jacob / Linda Barr Phone: 202 564 8019 / 202 564 7997 OMB 83 I 10/ 95 19. Certification for Paperwork Reduction Act Submissions On behalf of this Federal agency, 1 certify that the collection of information encompassed by this request complies with' 5 CFR 1320.9.

NOTE: The text of 5 CFR 1320.9, and the related provisions of 5 CFR 1320.8( b)( 3), appear at the end of the instructions. The certification is to be made with reference to those regulatory provisions as set forth in the instructions.

The following is a summary of the topics, regarding the proposed collection of information, that the certification covers:

( a) It is necessary for the proper performance of agency functions;

( b) It avoids unnecessary duplication;

( c) It reduces burden on small entities;

( d) It uses plain, coherent, and unambiguous terminology that is understandable to respondents;

( e) Its implementation will be consistent and compatible with current reporting and recordkeeping practices;

( f) It indicates the retention periods for recordkeeping requirements;

( g) It informs respondents of the information called for under 5 CFR 1320.8( b)( 3): ( I) Why the information is being collected' ( ii) Use of information; ( iii) Burden estimate; ( iv) Nature of response ( voluntary, required for a benefit, or mandatory); ( v) Nature and extent of confidentiality; and ( vi) Need to display currently valid OMB control number;

( h) It was developed by an office that has planned and allocated resources for the efficient and effective management and use of the information to be collected ( see note in Item 19 of the instructions);

( I) It uses effective and efficient statistical survey methodology; and ( j) It makes appropriate use of information technology.

If you are unable to certify compliance with any of these provisions, identify the item below and explain the reason in Item 18 of the Supporting Statement.

Signature of Program Official Date Signature of Senior Official or designee Oscar Morales, Director Collection Strategies Division Office of Environmental Information Date OMB 83 I 10/ 95 Certification Requirement for Paperwork Reduction Act Submissions 5 CFR 1320.9 reads " As part of the agency submission to OMB of a proposed collection of information, the agency ( through the head of the agency, the Senior Official or their designee) shall certify ( and provide a record supporting such certification) that the proposed collection of information

"( a) is necessary for the proper performance of the functions of the agency, including that the information to be collected will have practical utility;

"( b) is not unnecessarily duplicative of information otherwise reasonably accessible to the agency;

"( c) reduces to the extent practicable and appropriate the burden on persons who shall provide information to or for the agency, including with respect to small entities, as defined in the Regulatory Flexibility Act 5 U. S. C § 601( 6)), the use of such techniques as:

"( 1) establishing differing compliance or reporting requirements or timetables that take into account the resources available to those who are to respond; "( 2) the clarification, consolidation, or simplification of compliance and reporting requirements; or collection of information , or any part thereof; "( 3) an exemption from coverage of the collection of information, or any part thereof;

"( d) is written using plain, coherent, and unambiguous terminology and is understandable to those who are to respond;

"( e) is to be implemented in ways consistent and compatible, to the maximum extent practicable, with the existing reporting and recordkeeping practices of those who are to respond;

"( f) indicates for each recordkeeping requirement the length of time persons are required to maintain the records specified;

"( g) informs potential respondents of the information called for under § 1320.8( b)( 3); [ see below]

"( h) has been developed by an office that has planned and allocated resources for the efficient and effective management and use of the information to be collected, including the processing of the information in a manner which shall enhance, where appropriate, the utility of the information to agencies and the public;

"( I) uses effective and efficient statistical survey methodology appropriate to the purpose for which the information is to be collected; and "( j) to the maximum extent practicable, uses appropriate information technology to reduce burden and improve data quality, agency efficiency and responsiveness to the public."

NOTE: 5 CFR 1320.8( b)( 3) requires that each collection of information:

"( 3) informs and provides reasonable notice to the potential persons to whom the collection of information is addressed of: "( I) the reasons the information is planned to be and/ or has been used to further the proper performance of the functions of the agency; "( ii) the way such information is planned to be and/ or has been used to further the proper performance of the functions of the agency; "( iii) an estimate, to the extent practicable, of the average burden of the collection ( together with a request that the public direct to the agency any comments concerning the accuracy of this burden estimate and any suggestions for reducing this burden); "( iv) whether responses to the collection of information are voluntary, required to obtain or retain a benefit ( citing authority), or mandatory ( citing authority); "( v) the nature and extent of confidentiality to be provided, if any ( citing authority); and "( vi) the fact that any 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."

OMB 83 I ( Instructions) 10/ 95


Edits to Chapter VIII 1 4/ 9/ 2004 DRAFT for Internal Deliberation Do Not Cite or Quote VIII. Clarifications to January 30, 2004 Proposal This section provides clarifications to the proposed rule where the preamble language provided in the published proposal was unclear, inadvertently omitted, or inadvertently incorrect. Unless otherwise indicated, all references to the Federal Register   69 FR 4566 4650   are to the proposed Interstate Air Quality Rule ( IAQR).

A. States covered by the proposed action On 69 FR 4633 col. 1, EPA discussed the NOx cap and trade program. Under the heading " States Outside the Proposed Region with Existing Regional NOx Cap and Trade Programs", EPA mistakenly identified Massachusetts in a list of States that would not be affected by the proposed rules. Massachusetts should be deleted from that list because it would be affected by the proposed rules. | | On 69 FR 4584 col. 2, EPA discussed alternative significance levels for inclusion of | states in the IAQR. A level of 1% of the NAAQS for particulate matter was proposed, | and EPA solicited comments on higher and lower thresholds. Noting that a threshold of | 2 ppb was used for ozone, and that this level is 1.7% of the 1 hour average ozone | NAAQS and 2.5% of the 8 hour average NAAQS, EPA seeks comment specifically on | PM2.5 significance levels that would parallel the ozone percentages, i. e., 1.7% and | 2.5% of the PM2.5 NAAQS ( 0.25 and 0.375 ug/ m3). | | B. Source categories covered by the proposed action | | On 69 FR 4611 col. 3, EPA discussed alternative approaches to determining whether | source categories should be covered by the IAQR. We discussed our interpretation of | the " contribute significantly" determination under CAA section 110( a)( 2)( D), and the | fact that air quality component and the cost effectiveness component of that | determination. In short, we stated that a broad multi state call for SIP revisions to | address interstate transport of air pollution is warranted only for groups of sources | make substantial contributions to a significant number of nonattainment areas. Other | mechanisms exist to address isolated instances of interstate transport, such as SIP | disapproval authority and state petitions under Section 126 of the Clean Air Act. | | One approach cited in the NOPR for ensuring that both the air quality component and | the cost effectiveness component of the " contribute significantly" determination is met, | is to consider a source category's contribution to ambient concentrations above the | attainment level in all nonattainment areas in affected downwind states. EPA | furthermore seeks comment on a variation on this concept: that is, whether a source | category should be considered to meet the " contribute significantly" requirement only if | the proposed level of additional control of that category would result in at least 0.5% of | U. S. counties coming into attainment with a NAAQS. Given the number of counties and | parishes in the U. S., this would be at least 16 counties. Control of EGUs in the IAQR | meets this test. EPA believes that the " contribute significantly" requirement should | include this test because if control of a source category did not bring into NAAQS | attainment at least 0.5% of the Nation's counties, then the category would not be | significant enough to warrant a unique Federally driven, multi state mitigation program. | As with the other criteria in this call for SIP revisions, use of this criteria in defining a | Federal multi state SIP call in no way limits a State's responsibilities under the Clean | Air Act, including under section 110( a)( 2)( D). | | | [ Re letter subsequent paragraphs.] |

B. Summary of control costs The control cost summary provided on 69 FR 4632 col. 2 ( first full paragraph) indicates a marginal cost per ton of SO2 emissions of $ 805 in the first phase, and $ 989 in the second phase, of the proposed control program. These


[Federal Register Volume 77, Number 101 (Thursday, May 24, 2012)]
[Notices]
[Pages 31022-31024]
[FR Doc No: 2012-12590]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2012-N-0477]

Agency Information Collection Activities; Proposed Collection;
Comment Request; Investigational Device Exemptions Reports and Records

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 investigational device
exemptions reports and records.

DATES: Submit either electronic or written comments on the collection
of information by July 23, 2012.

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: Daniel Gittleson, 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.

Investigational Device Exemptions Reports and Records--21 CFR Part 812
(OMB Control Number 0910-0078)--Extension

    Section 520(g) of the Federal Food, Drug, and Cosmetic Act (the
FD&C Act) (21 U.S.C. 360j(g)) establishes the statutory authority to
collect information regarding investigational devices, and establishes
rules under which new medical devices may be tested using human
subjects in a clinical setting. The Food and Drug Administration
Modernization Act of 1997 (Pub. L. 105-115) added section 520(g)(6) to
the FD&C Act and permitted changes to be made to either the
investigational device or to the clinical protocol without FDA approval
of an investigational device exemption (IDE) supplement. An IDE allows
a device, which would otherwise be subject to provisions of the FD&C
Act, such as premarket notification or premarket approval, to be used
in investigations involving human subjects in which the safety and
effectiveness of the device is being studied. The purpose of part 812
(21 CFR part 812) is to encourage, to the extent consistent with the
protection of public health and safety and with ethical standards, the
discovery and development of useful devices intended for human use. The
IDE regulation is designed to encourage the development of useful
medical devices and allow investigators the maximum freedom possible,
without jeopardizing the health and safety of the public or violating
ethical standards. To do this, the regulation provides for different
levels of regulatory control depending on the level of potential risk
the investigational device presents to human subjects. Investigations
of significant risk devices, ones that present a potential for serious
harm to the rights, safety, or welfare of human subjects, are subject
to the full requirements of the IDE regulation. Nonsignificant risk
device investigations, i.e., devices that do not present a potential
for serious harm, are subject to the reduced burden of the abbreviated
requirements. The regulation also includes provisions for treatment
IDEs. The purpose of these provisions is to facilitate the
availability, as early in the device development process as possible,
of promising new devices to patients with life-threatening or serious
conditions for which no comparable or satisfactory alternative therapy
is available. Section 812.10 permits the sponsor of the IDE to request
a waiver to all of the requirements of part 812. This information is
needed for FDA to determine if waiver of the requirements of part 812
will impact the public's health and safety. Sections 812.20, 812.25,
and 812.27 consist of the information necessary to file an IDE
application with FDA. The submission of an IDE application to FDA is
required only for significant risk device investigations.
    Section 812.20 lists the data requirements for the original IDE
application; Sec.  812.25 lists the contents of the investigational
plan; and Sec.  812.27 lists the data relating to previous
investigations or testing. The information in the original IDE
application is evaluated by the Center for Devices and Radiological
Health to determine whether the proposed investigation will reasonably
protect the public health and safety, and for FDA to make a
determination to approve the IDE.
    Upon approval of an IDE application by FDA, a sponsor must submit
certain requests and reports. Under Sec.  812.35, a sponsor who wishes
to make a change in the investigation that affects the scientific
soundness of the study or the rights, safety, or welfare of the
subjects, is required to submit a request for the change to FDA.
Section 812.150 requires a sponsor to submit reports to FDA.

These requests and reports are submitted to FDA as supplemental
applications. This information is needed for FDA to assure protection
of human subjects and to allow review of the study's progress. Section
812.36(c) identifies the information necessary to file a treatment IDE
application. FDA uses this information to determine if wider
distribution of the device is in the interest of the public health.
Section 812.36(f) identifies the reports required to allow FDA to
monitor the size and scope of the treatment IDE, to assess the
sponsor's due diligence in obtaining marketing clearance of the device
and to ensure the integrity of the controlled clinical trials.
    FDA estimates the burden of this collection of information as
follows:

                                 Table 1--Estimated Annual Reporting Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
     Activity/21 CFR section         Number of     responses per   Total annual     burden per      Total hours
                                    respondents     respondent       responses       response
----------------------------------------------------------------------------------------------------------------
Waivers/812.10..................               1               1               1               1               1
IDE application/812.20, 812.25,              356               1             356              80          28,480
 and 812.27.....................
Supplements/812.35 and 812.150..             356              12           4,272               6          25,632
Treatment IDE applications/                    1               1               1             120             120
 812.36(c)......................
Treatment IDE reporting/                       1               1               1              20              20
 812.36(f)......................
                                 -------------------------------------------------------------------------------
    Total.......................  ..............  ..............  ..............  ..............          54,253
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    Section 812.140 lists the recordkeeping requirements for
investigators and sponsors. FDA requires this information for tracking
and oversight purposes. Investigators are required to maintain records,
including correspondence and reports concerning the study, records of
receipt, use or disposition of devices, records of each subject's case
history and exposure to the device, informed consent documentation,
study protocol, and documentation of any deviation from the protocol.
Sponsors are required to maintain records including correspondence and
reports concerning the study, records of shipment and disposition,
signed investigator agreements, adverse device effects information,
and, for a nonsignificant risk device study, an explanation of the
nonsignificant risk determination, records of device name and intended
use, study objectives, investigator information, investigational review
board information, and statement on the extent that good manufacturing
practices will be followed.

                               Table 2--Estimated Annual Recordkeeping Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
     Activity/21 CFR section         Number of      records per    Total annual     burden per      Total hours
                                   recordkeepers   recordkeeper       records      recordkeeping
----------------------------------------------------------------------------------------------------------------
Original/812.140................             356               1             356              10           3,560
Supplemental/812.140............             356              12           4,272               1           4,272
Nonsignificant/812.140..........             356               1             356               6           2,136
                                 -------------------------------------------------------------------------------
    Totals......................  ..............  ..............  ..............  ..............           9,968
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    For a nonsignificant risk device investigation, the investigator's
and sponsor's recordkeeping and reporting burden is reduced. Pertinent
records on the study must be maintained by both parties, and reports
are made to sponsors and institutional review boards (IRBs). Reports
are made to FDA only in certain circumstances, e.g., recall of the
device, the occurrence of unanticipated adverse effects, and as a
consequence of certain IRB actions.

                           Table 3--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
                                                     Number of                        Average
     Activity/21 CFR section         Number of      disclosures    Total annual     burden per      Total hours
                                    respondents   per respondent    disclosures     disclosure
----------------------------------------------------------------------------------------------------------------
Reports for Nonsignificant Risk                1               1               1               6               6
 Studies/812.150................
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
  information.

    The estimate of the burden is based on the number of IDEs received
in the last 3 years.

    Dated: May 17, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-12590 Filed 5-23-12; 8:45 am]
BILLING CODE 4160-01-P