Good Laboratory Practice for Nonclinical Laboratory Studies, 80011-80013 [2010-31888]
Download as PDF
<![CDATA[
Federal Register / Vol. 75, No. 244 / Tuesday, December 21, 2010 / Proposed Rules
(v) Means other than those described
in paragraphs (a)(5)(i), (ii), (iii), and (iv)
of this section;
(6) Whether the counterparty invoking
1. The authority citation for part 240
the clearing exception is an issuer of
is amended by adding the following
securities registered under Section 12
citation in numerical order to read as
(15 U.S.C. 78l) or subject to reporting
follows:
requirements pursuant to Section 15(d)
Authority: 15 U.S.C. 77c, 77d, 77g, 77j,
(15 U.S.C. 78o(d)) of the Act, and if so:
77s, 77z–2, 77z–3, 77eee, 77ggg, 77nnn,
77sss, 77ttt, 78c, 78d, 78e, 78f, 78g, 78i, 78j,
(i) The relevant Commission Central
78j–1, 78k, 78k–1, 78l, 78m, 78n, 78o, 78o–
Index Key number for the counterparty
4, 78p, 78q, 78s, 78u–5, 78w, 78x, 78ll,
invoking the clearing exception; and
78mm, 80a–20, 80a–23, 80a–29, 80a–37, 80b–
(ii) Whether an appropriate committee
3, 80b–4, 80b–11, and 7201 et seq.; 18 U.S.C.
1350; and 12 U.S.C. 5221(e)(3), unless
of the board of directors (or equivalent
otherwise noted.
body) of the counterparty invoking the
clearing exception has reviewed and
*
*
*
*
*
approved the decision to enter into a
Section 240.3Cg–1 is also issued under
security-based swap subject to the
Public Law 111–203, § 763, 124 Stat. 1841
(2010).
clearing exception.
*
*
*
*
*
Additional Rule Text Under
PART 240—GENERAL RULES AND
REGULATIONS, SECURITIES
EXCHANGE ACT OF 1934
2. Add § 240.3Cg–1 to read as follows:
jlentini on DSKJ8SOYB1PROD with PROPOSALS
§ 240.3Cg–1 Notice to the Commission
[and Financial Entity Exemption].
(a) A counterparty to a security-based
swap that invokes the clearing
exception under Section 3C(g)(1) of the
Act (15 U.S.C. 78c–3(g)(1)) shall satisfy
the requirements of Section 3C(g)(1)(C)
of the Act (15 U.S.C. 78c–3(g)(1)(C)) by
delivering or causing to be delivered the
following additional information to a
registered security-based swap data
repository (or, if none is available, to the
Commission) in the form and manner
required for delivery of the information
separately specified under § 242.901(d)
of Regulation SBSR of this chapter:
(1) The identity of the counterparty
relying on the clearing exception;
(2) Whether the counterparty invoking
the clearing exception is a ‘‘financial
entity’’ as defined in Section 3C(g)(3) of
the Act (15 U.S.C. 78c–3(g)(3));
(3) Whether the counterparty invoking
the clearing exception is a finance
affiliate meeting the requirements
described in Section 3C(g)(4) of the Act
(15 U.S.C. 78c–3(g)(4));
(4) Whether the security-based swap
is used by the counterparty invoking the
clearing exception to hedge or mitigate
commercial risk as defined in
§ 240.3a67–4 of this chapter;
(5) Whether the counterparty invoking
the clearing exception generally expects
to meet its financial obligations
associated with the security-based swap
by using any of the following:
(i) A written credit support
agreement;
(ii) A written agreement to pledge or
segregate assets;
(iii) A written third-party guarantee;
(iv) Solely the counterparty’s
available financial resources; or
VerDate Mar<15>2010
16:24 Dec 20, 2010
Jkt 223001
Consideration by the Commission
(b) For purposes of Section
3C(g)(1)(A) of the Act (15 U.S.C. 78c–
3(g)(1)(A)), any person specified in
paragraph (c) of this section that would
be a financial entity within the meaning
of the term in Section 3C(g)(3)(A) of the
Act (15 U.S.C. 78c–3(g)(3)(A)) solely
because of Section 3C(g)(3)(A)(viii) of
the Act (15 U.S.C. 78c–3(g)(3)(A)(viii))
shall be exempt from the definition of
financial entity.
(c) A person shall be eligible for the
exemption in paragraph (b) of this
section if such person:
(1) Is organized as a bank, as defined
in Section 3(a)(6) of the Act (15 U.S.C.
78c), the deposits of which are insured
by the Federal Deposit Insurance
Corporation, a savings association, as
defined in section 3(b) of the Federal
Deposit Insurance Act (12 U.S.C. 1831),
the deposits of which are insured by the
Federal Deposit Insurance Corporation,
a farm credit system institution
chartered under the Farm Credit Act of
1971 (12 U.S.C. 2001), or an insured
Federal credit union or State-chartered
credit union under the Federal Credit
Union Act (12 U.S.C. 1752); and
(2) Has total assets of $10,000,000,000
or less on the last day of the most recent
fiscal year.
By the Commission.
Dated: December 15, 2010.
Elizabeth M. Murphy,
Secretary.
[FR Doc. 2010–31973 Filed 12–20–10; 8:45 am]
BILLING CODE 8011–01–P
PO 00000
Frm 00030
Fmt 4702
Sfmt 4702
80011
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Part 58
[Docket No. FDA–2010–N–0548]
Good Laboratory Practice for
Nonclinical Laboratory Studies
AGENCY:
Food and Drug Administration,
HHS.
Advance notice of proposed
rulemaking.
ACTION:
The Food and Drug
Administration (FDA) is seeking
comment on whether to amend the
regulations governing good laboratory
practices (GLPs). The Agency decided
that to require a GLP quality system for
all facilities/laboratories, as well as to
more completely address nonclinical
studies as they are presently conducted,
the Agency would need to modify the
existing regulations.
DATES: Submit either electronic or
written comments by February 22, 2011.
ADDRESSES: You may submit comments,
identified by the Docket No. FDA–2010–
N–0548, by any of the following
methods:
SUMMARY:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the
instructions for submitting comments.
Written Submissions
Submit written submissions in the
following ways:
• Fax: 301–827–6870.
• Mail/Hand delivery/Courier (for
paper, disk, or CD–ROM submissions):
Division of Dockets Management (HFA–
305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852.
Instructions: All submissions received
must include the Agency name and
docket number for this rulemaking. All
comments received may be posted
without change to https://
www.regulations.gov, including any
personal information provided. For
additional information on submitting
comments, see the ‘‘Comments’’ heading
of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: For access to the docket to
read background documents or
comments received, go to https://
www.regulations.gov and insert the
docket number, found in the brackets in
the heading of this document, into the
‘‘Search’’ box and follow the prompts
E:\FR\FM\21DEP1.SGM
21DEP1
80012
Federal Register / Vol. 75, No. 244 / Tuesday, December 21, 2010 / Proposed Rules
and/or go to the Division of Dockets
Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: C. T.
Viswanathan, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5346,
Silver Spring, MD 20993–0002, 301–
796–3394.
SUPPLEMENTARY INFORMATION:
jlentini on DSKJ8SOYB1PROD with PROPOSALS
I. Background
FDA’s GLP regulations, part 58 (21
CFR part 58), were finalized on
December 22, 1978 (43 FR 60013). As
stated in its scope (§ 58.1), this
regulation prescribes good laboratory
practices for conducting nonclinical
laboratory studies that support or are
intended to support applications for
research or marketing permits for
products regulated by FDA, including
food and color additives, animal food
additives, human and animal drugs,
medical devices for human use,
biological products, and electronic
products. A nonclinical laboratory
study, as defined in § 58.3(d), is an
* * * in vivo or in vitro experiment in
which test articles are studied
prospectively in test systems under
laboratory conditions to determine their
safety. The term does not include
studies utilizing human subjects or
clinical studies or field trials in animals.
[It also] does not include basic
exploratory studies carried out to
determine whether a test article has any
potential utility or to determine
physical or chemical characteristics of a
test article.
The conduct of nonclinical laboratory
studies has changed markedly since
issuance of this regulation in 1978. For
example, it is presently common for
nonclinical laboratory studies to be
conducted across multiple testing
facilities, or sites (multisite studies).
When the regulation was originally
finalized, however, most studies were
conducted within a single facility. In
addition, laboratories have expanded
the use of electronic technology, both
for laboratory instrumentation and as a
means for collecting, storing, and
reporting study data. Current part 58
does not specifically describe these
modern arrangements and advances.
In 2006, FDA announced its Human
Subject Protection/Bioresearch
Monitoring (HSP/BIMO) initiative
aimed at modernizing the Agency’s
regulations and policies governing the
conduct of studies used to support
submissions to FDA. In response to the
announcement of the HSP/BIMO
initiative, FDA received stakeholder
VerDate Mar<15>2010
16:24 Dec 20, 2010
Jkt 223001
recommendations that included
suggestions for the revision of part 58.
In 2007, FDA established an Agencywide GLP working group (WG) to
evaluate the existing regulation and
determine if regulatory revision and/or
guidance should be pursued. The WG
gathered information as to the needs of
each FDA center with regard to
nonclinical laboratory studies, reviewed
suggestions from external sources,
conferred with the Environmental
Protection Agency (EPA) which has a
similar regulation, and performed a
thorough evaluation of the existing
regulations. The WG concluded that to
ensure the integrity of the data in all
nonclinical laboratory studies submitted
to FDA, nonclinical laboratory facilities
that conduct these studies need to
follow a GLP quality system approach.
Currently, the regulations governing
nonclinical laboratory studies do not
use such an approach consistently
throughout part 58. A GLP quality
system would allow nonclinical
laboratories to develop standard
operating procedures consistent with
their specific operational needs as long
as they satisfy regulatory requirements
aimed at ensuring data integrity. The
WG decided that to require a GLP
quality system for all facilities/
laboratories, as well as to more
completely address nonclinical studies
as they are presently conducted, the
Agency would need to modify the
existing regulations.
II. Agency Request for Information
FDA is soliciting public comments
about whether to modify the existing
regulations, and in particular about the
areas FDA has identified as potentially
appropriate for revision, as follows:
1. GLP Quality System
While many of the requirements of
the existing regulation are consistent
with a GLP quality system, FDA
believes that modifications may be
necessary to incorporate all basic
elements needed for a comprehensive
GLP quality system, such as that set
forth in the internationally recognized
standard, Quality management
systems—Requirements ISO 9001,
available from the International
Organization for Standardization (ISO)
at: https://www.iso.org/iso/home.html.
Ultimately, any GLP quality system
proposed for a facility must be capable
of ensuring the integrity of resulting
data. FDA is considering whether to
include in the regulations a core set of
essential elements for such a GLP
quality system, including specifically
mentioning management responsibility
for all activities at the facility and
PO 00000
Frm 00031
Fmt 4702
Sfmt 4702
specifying a requirement for standard
operating procedures for all essential
functions.
2. Multisite Studies
It is currently common practice for
nonclinical laboratory studies to be
performed across multiple sites
(multisite studies), rather than for a
single facility to conduct all aspects/
phases of a study. FDA is considering
revising the GLP regulations to
specifically address the use of multisite
studies through the addition of specific
definitions to describe personnel and
study aspects specific to multisite
studies, e.g., by requiring that an
individual be designated as the
responsible person for each site of a
multisite study. Such an individual
would be responsible for any phase(s) of
the study conducted at the site and
would report to the study director.
3. Electronic/Computerized Systems
Since the regulation was finalized,
many laboratory systems have become
fully automated. In addition, many
facilities now employ computerized
systems for managing general laboratory
functions as well as for instrumentation
in which such systems are integral
components. While the present
regulation does not preclude such
electronic systems, several of the
current regulatory requirements are
more consistent with paper-based
systems (e.g., an individual as archivist
§ 58.190(c)); maintenance of copies of
study protocols and the Master
Schedule by the quality assurance unit
(§ 58.35(b)(1) and (b)(2))). FDA is
considering updating the regulation to
reflect the use of electronic and
computerized systems. FDA believes
that any modifications to the regulation
to reference electronic/computerized
systems should be general, to
accommodate changes and advances in
technology.
4. Sponsor Responsibilities
Whether nonclinical laboratory
studies are conducted by a sponsor or at
a contracted facility, FDA believes that
the study sponsor should clearly have
responsibilities that the present
regulation does not specifically
mention, such as development and/or
approval of study protocols. FDA is
therefore considering amending the
regulations to include additional
specific responsibilities of sponsors of
nonclinical laboratory studies.
5. Animal Welfare
In the United States, the Animal
Welfare Act (7 U.S.C 2131–2159)
governs the treatment and use of
E:\FR\FM\21DEP1.SGM
21DEP1
Federal Register / Vol. 75, No. 244 / Tuesday, December 21, 2010 / Proposed Rules
animals, including their use for research
purposes. FDA is soliciting comments
regarding whether and how to receive
documentation of compliance with
these existing statutory provisions or
comparable international standards
governing the ethical and humane use of
laboratory animals in nonclinical
laboratory studies. This issue is not
specifically addressed in the present
regulation.
jlentini on DSKJ8SOYB1PROD with PROPOSALS
6. Information on Quality Assurance
Inspectional Findings
When an FDA bioresearch monitoring
(BIMO) inspection of a nonclinical
study identifies problems, FDA often
finds it difficult to determine whether
the quality assurance unit (QAU) failed
to adequately inspect the study, or
whether the QAU made
recommendations for corrective actions
and management did not adequately
respond. FDA is considering the
addition of a requirement that the QAU
prepare a yearly summary of general
inspectional findings that would reveal
problems that are not necessarily studyspecific and that includes the
recommendations made to management
to resolve those problems. Such a report
would be maintained at the facility and
be made available to FDA upon request,
usually during the course of a BIMO
inspection.
7. Process-Based Systems Inspections
A number of procedures used in
conducting a particular nonclinical
laboratory study are common across
many or even most studies conducted at
the facility. Facilities often find it more
resourceful to periodically inspect such
procedures during systems inspections
rather than repetitively as part of each
study-specific inspection, as currently
required in § 58.35(b). For example, it
may be appropriate to periodically
inspect procedures such as slide
preparation for pathology studies as part
of a facility’s process-based systems
inspections rather than for each study.
FDA therefore is considering permitting
a combination of systems inspections
and study-specific inspections. The
results of the appropriate systems
inspection(s) would be referenced in the
study-specific inspection reports
relevant to those aspects of the
procedures for the study under
inspection.
8. Test and Control Article Information
When reviewing and inspecting
nonclinical laboratory studies,
particularly those submitted for new
drugs (human and animal), basic
information about the test article, such
as strength, purity, stability, and for
VerDate Mar<15>2010
16:24 Dec 20, 2010
Jkt 223001
mixtures thereof, concentration and
uniformity, is often absent from the
laboratory’s records, therefore
precluding appropriate interpretation of
the study results. Although the current
regulations require that these
parameters be determined (§ 58.105(a)
and (b) and § 58.113(a)), the regulations
do not specify who is to receive this
information or include a timeframe for
delivery of the information to the
facility performing the nonclinical
testing. FDA is therefore considering
additional requirements under the
sections in the regulations discussing
test and control characterization
(§ 58.105) and mixtures of articles with
carriers (§ 58.113), including timeframes
for provision of this information to the
study director.
In addition, sponsors have requested
the ability to cite compliance with the
applicable good manufacturing
requirements (i.e, parts 210 and 211, etc.
as relevant) regarding the specifications,
quality, and integrity of the test article.
FDA is considering whether to accept
compliance with either the specifics
that would be required under a revised
part 58, subpart F or the relevant good
manufacturing requirements.
9. Sample Storage Container Retention
FDA’s regulations currently require
that facilities maintain test article
storage containers for the duration of the
study (21 CFR 58.105(c)). FDA believes
that compliance with the regulatory
requirements for the handling of test
and control articles, which include
documentation of receipt, distribution,
and use of each batch (§ 58.107(d))
provides adequate information about the
use and integrity of study samples.
Therefore, FDA is considering
eliminating the requirement at
§ 58.105(c).
FDA welcomes comments from all
interested persons on these issues and
any other concerns related to the current
GLP regulations, including
recommendations as to the best
method(s) for addressing such concerns.
III. Comments
Interested persons may submit to the
Division of Dockets Management (see
ADDRESSES) either electronic or written
comments regarding this document.
Identify comments with the docket
number found in brackets in the
heading of this document. Received
comments may be seen in the Division
of Dockets Management between 9 a.m.
and 4 p.m., Monday through Friday.
This advance notice of proposed
rulemaking is issued under section 201
et al. of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321 et al.) and
PO 00000
Frm 00032
Fmt 4702
Sfmt 9990
80013
under authority of the Commissioner of
Food and Drugs.
Dated: December 15, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–31888 Filed 12–20–10; 8:45 am]
BILLING CODE 4160–01–P
FEDERAL COMMUNICATIONS
COMMISSION
47 CFR Part 73
[DA 10–2279; MB Docket No. 10–65; RM–
10595]
Radio Broadcasting Services; Jewett,
TX
Federal Communications
Commission.
ACTION: Proposed rule; dismissal.
AGENCY:
At the petitioner’s request, the
Audio Division has dismissed the
proposal of Charles Crawford to allot
Channel 232A at Jewett, Texas.
Crawford had filed a petition for rule
making proposing the allotment of
Channel 232A at Jewett, Texas, as the
community’s first local FM transmission
service.
FOR FURTHER INFORMATION CONTACT:
Deborah Dupont, Media Bureau, (202)
418–2180.
SUPPLEMENTARY INFORMATION: This is a
synopsis of the Commission’s Report
and Order, MB Docket No. 10–65, RM–
10595, adopted December 1, 2010, and
released December 3, 2010. The full text
of this Commission decision is available
for inspection and copying during
normal business hours in the FCC
Reference Information Center, Portals II,
445 12th Street, SW., Room CY–A257,
Washington, DC 20554. The complete
text of this decision also may be
purchased from the Commission’s
duplicating contractor, Best Copy and
Printing, Inc., 445 12th Street, SW.,
Room CY–B402, Washington, DC 20554,
(800) 378–3160, or via the company’s
Web site, https://www.bcpiweb.com. This
document is not subject to the
Congressional Review Act. The
Commission is, therefore, not required
to send a copy of this Report and Order
in a report to be sent to Congress and
the Government Accountability Office
pursuant to the Congressional Review
Act, see U.S.C. 801(a)(1)(A), because the
proposed rule was dismissed.
SUMMARY:
Federal Communications Commission.
John A. Karousos,
Assistant Chief, Audio Division, Media
Bureau.
[FR Doc. 2010–31997 Filed 12–20–10; 8:45 am]
BILLING CODE 6712–01–P
E:\FR\FM\21DEP1.SGM
21DEP1
]]>Agencies
[Federal Register Volume 75, Number 244 (Tuesday, December 21, 2010)]
[Proposed Rules]
[Pages 80011-80013]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-31888]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 58
[Docket No. FDA-2010-N-0548]
Good Laboratory Practice for Nonclinical Laboratory Studies
AGENCY: Food and Drug Administration, HHS.
ACTION: Advance notice of proposed rulemaking.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is seeking comment on
whether to amend the regulations governing good laboratory practices
(GLPs). The Agency decided that to require a GLP quality system for all
facilities/laboratories, as well as to more completely address
nonclinical studies as they are presently conducted, the Agency would
need to modify the existing regulations.
DATES: Submit either electronic or written comments by February 22,
2011.
ADDRESSES: You may submit comments, identified by the Docket No. FDA-
2010-N-0548, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments.
Written Submissions
Submit written submissions in the following ways:
Fax: 301-827-6870.
Mail/Hand delivery/Courier (for paper, disk, or CD-ROM
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Instructions: All submissions received must include the Agency name
and docket number for this rulemaking. All comments received may be
posted without change to https://www.regulations.gov, including any
personal information provided. For additional information on submitting
comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: For access to the docket to read background documents or
comments received, go to https://www.regulations.gov and insert the
docket number, found in the brackets in the heading of this document,
into the ``Search'' box and follow the prompts
[[Page 80012]]
and/or go to the Division of Dockets Management, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: C. T. Viswanathan, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5346, Silver Spring, MD 20993-0002, 301-
796-3394.
SUPPLEMENTARY INFORMATION:
I. Background
FDA's GLP regulations, part 58 (21 CFR part 58), were finalized on
December 22, 1978 (43 FR 60013). As stated in its scope (Sec. 58.1),
this regulation prescribes good laboratory practices for conducting
nonclinical laboratory studies that support or are intended to support
applications for research or marketing permits for products regulated
by FDA, including food and color additives, animal food additives,
human and animal drugs, medical devices for human use, biological
products, and electronic products. A nonclinical laboratory study, as
defined in Sec. 58.3(d), is an * * * in vivo or in vitro experiment in
which test articles are studied prospectively in test systems under
laboratory conditions to determine their safety. The term does not
include studies utilizing human subjects or clinical studies or field
trials in animals. [It also] does not include basic exploratory studies
carried out to determine whether a test article has any potential
utility or to determine physical or chemical characteristics of a test
article.
The conduct of nonclinical laboratory studies has changed markedly
since issuance of this regulation in 1978. For example, it is presently
common for nonclinical laboratory studies to be conducted across
multiple testing facilities, or sites (multisite studies). When the
regulation was originally finalized, however, most studies were
conducted within a single facility. In addition, laboratories have
expanded the use of electronic technology, both for laboratory
instrumentation and as a means for collecting, storing, and reporting
study data. Current part 58 does not specifically describe these modern
arrangements and advances.
In 2006, FDA announced its Human Subject Protection/Bioresearch
Monitoring (HSP/BIMO) initiative aimed at modernizing the Agency's
regulations and policies governing the conduct of studies used to
support submissions to FDA. In response to the announcement of the HSP/
BIMO initiative, FDA received stakeholder recommendations that included
suggestions for the revision of part 58. In 2007, FDA established an
Agency-wide GLP working group (WG) to evaluate the existing regulation
and determine if regulatory revision and/or guidance should be pursued.
The WG gathered information as to the needs of each FDA center with
regard to nonclinical laboratory studies, reviewed suggestions from
external sources, conferred with the Environmental Protection Agency
(EPA) which has a similar regulation, and performed a thorough
evaluation of the existing regulations. The WG concluded that to ensure
the integrity of the data in all nonclinical laboratory studies
submitted to FDA, nonclinical laboratory facilities that conduct these
studies need to follow a GLP quality system approach. Currently, the
regulations governing nonclinical laboratory studies do not use such an
approach consistently throughout part 58. A GLP quality system would
allow nonclinical laboratories to develop standard operating procedures
consistent with their specific operational needs as long as they
satisfy regulatory requirements aimed at ensuring data integrity. The
WG decided that to require a GLP quality system for all facilities/
laboratories, as well as to more completely address nonclinical studies
as they are presently conducted, the Agency would need to modify the
existing regulations.
II. Agency Request for Information
FDA is soliciting public comments about whether to modify the
existing regulations, and in particular about the areas FDA has
identified as potentially appropriate for revision, as follows:
1. GLP Quality System
While many of the requirements of the existing regulation are
consistent with a GLP quality system, FDA believes that modifications
may be necessary to incorporate all basic elements needed for a
comprehensive GLP quality system, such as that set forth in the
internationally recognized standard, Quality management systems--
Requirements ISO 9001, available from the International Organization
for Standardization (ISO) at: https://www.iso.org/iso/home.html.
Ultimately, any GLP quality system proposed for a facility must be
capable of ensuring the integrity of resulting data. FDA is considering
whether to include in the regulations a core set of essential elements
for such a GLP quality system, including specifically mentioning
management responsibility for all activities at the facility and
specifying a requirement for standard operating procedures for all
essential functions.
2. Multisite Studies
It is currently common practice for nonclinical laboratory studies
to be performed across multiple sites (multisite studies), rather than
for a single facility to conduct all aspects/phases of a study. FDA is
considering revising the GLP regulations to specifically address the
use of multisite studies through the addition of specific definitions
to describe personnel and study aspects specific to multisite studies,
e.g., by requiring that an individual be designated as the responsible
person for each site of a multisite study. Such an individual would be
responsible for any phase(s) of the study conducted at the site and
would report to the study director.
3. Electronic/Computerized Systems
Since the regulation was finalized, many laboratory systems have
become fully automated. In addition, many facilities now employ
computerized systems for managing general laboratory functions as well
as for instrumentation in which such systems are integral components.
While the present regulation does not preclude such electronic systems,
several of the current regulatory requirements are more consistent with
paper-based systems (e.g., an individual as archivist Sec. 58.190(c));
maintenance of copies of study protocols and the Master Schedule by the
quality assurance unit (Sec. 58.35(b)(1) and (b)(2))). FDA is
considering updating the regulation to reflect the use of electronic
and computerized systems. FDA believes that any modifications to the
regulation to reference electronic/computerized systems should be
general, to accommodate changes and advances in technology.
4. Sponsor Responsibilities
Whether nonclinical laboratory studies are conducted by a sponsor
or at a contracted facility, FDA believes that the study sponsor should
clearly have responsibilities that the present regulation does not
specifically mention, such as development and/or approval of study
protocols. FDA is therefore considering amending the regulations to
include additional specific responsibilities of sponsors of nonclinical
laboratory studies.
5. Animal Welfare
In the United States, the Animal Welfare Act (7 U.S.C 2131-2159)
governs the treatment and use of
[[Page 80013]]
animals, including their use for research purposes. FDA is soliciting
comments regarding whether and how to receive documentation of
compliance with these existing statutory provisions or comparable
international standards governing the ethical and humane use of
laboratory animals in nonclinical laboratory studies. This issue is not
specifically addressed in the present regulation.
6. Information on Quality Assurance Inspectional Findings
When an FDA bioresearch monitoring (BIMO) inspection of a
nonclinical study identifies problems, FDA often finds it difficult to
determine whether the quality assurance unit (QAU) failed to adequately
inspect the study, or whether the QAU made recommendations for
corrective actions and management did not adequately respond. FDA is
considering the addition of a requirement that the QAU prepare a yearly
summary of general inspectional findings that would reveal problems
that are not necessarily study-specific and that includes the
recommendations made to management to resolve those problems. Such a
report would be maintained at the facility and be made available to FDA
upon request, usually during the course of a BIMO inspection.
7. Process-Based Systems Inspections
A number of procedures used in conducting a particular nonclinical
laboratory study are common across many or even most studies conducted
at the facility. Facilities often find it more resourceful to
periodically inspect such procedures during systems inspections rather
than repetitively as part of each study-specific inspection, as
currently required in Sec. 58.35(b). For example, it may be
appropriate to periodically inspect procedures such as slide
preparation for pathology studies as part of a facility's process-based
systems inspections rather than for each study. FDA therefore is
considering permitting a combination of systems inspections and study-
specific inspections. The results of the appropriate systems
inspection(s) would be referenced in the study-specific inspection
reports relevant to those aspects of the procedures for the study under
inspection.
8. Test and Control Article Information
When reviewing and inspecting nonclinical laboratory studies,
particularly those submitted for new drugs (human and animal), basic
information about the test article, such as strength, purity,
stability, and for mixtures thereof, concentration and uniformity, is
often absent from the laboratory's records, therefore precluding
appropriate interpretation of the study results. Although the current
regulations require that these parameters be determined (Sec.
58.105(a) and (b) and Sec. 58.113(a)), the regulations do not specify
who is to receive this information or include a timeframe for delivery
of the information to the facility performing the nonclinical testing.
FDA is therefore considering additional requirements under the sections
in the regulations discussing test and control characterization (Sec.
58.105) and mixtures of articles with carriers (Sec. 58.113),
including timeframes for provision of this information to the study
director.
In addition, sponsors have requested the ability to cite compliance
with the applicable good manufacturing requirements (i.e, parts 210 and
211, etc. as relevant) regarding the specifications, quality, and
integrity of the test article. FDA is considering whether to accept
compliance with either the specifics that would be required under a
revised part 58, subpart F or the relevant good manufacturing
requirements.
9. Sample Storage Container Retention
FDA's regulations currently require that facilities maintain test
article storage containers for the duration of the study (21 CFR
58.105(c)). FDA believes that compliance with the regulatory
requirements for the handling of test and control articles, which
include documentation of receipt, distribution, and use of each batch
(Sec. 58.107(d)) provides adequate information about the use and
integrity of study samples. Therefore, FDA is considering eliminating
the requirement at Sec. 58.105(c).
FDA welcomes comments from all interested persons on these issues
and any other concerns related to the current GLP regulations,
including recommendations as to the best method(s) for addressing such
concerns.
III. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. Identify comments with the docket number found in brackets in
the heading of this document. Received comments may be seen in the
Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
This advance notice of proposed rulemaking is issued under section
201 et al. of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321
et al.) and under authority of the Commissioner of Food and Drugs.
Dated: December 15, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010-31888 Filed 12-20-10; 8:45 am]
BILLING CODE 4160-01-P
