[Federal Register Volume 75, Number 244 (Tuesday, December 21, 2010)]
[Proposed Rules]
[Pages 80011-80013]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2010-31888]
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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.
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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: http://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 http://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 http://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: http://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
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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