[Federal Register Volume 73, Number 227 (Monday, November 24, 2008)]
[Notices]
[Pages 71003-71004]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-27790]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Toxicology Program (NTP); NTP Interagency Center for the
Evaluation of Alternative Toxicological Methods (NICEATM); Availability
of the Interagency Coordinating Committee on the Validation of
Alternative Methods (ICCVAM) Test Method Evaluation Report: Validation
Status of Five In Vitro Test Methods Proposed for Assessing Potential
Pyrogenicity of Pharmaceuticals and Other Products and Final Background
Review Document: Validation Status of Five In Vitro Test Methods
Proposed for Assessing Potential Pyrogenicity of Pharmaceuticals and
Other Products; Notice of Transmittal of ICCVAM Test Method
Recommendations to Federal Agencies
AGENCY: National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH)
ACTION: Availability of the ICCVAM Test Method Evaluation Report and
Final Background Review Document.
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SUMMARY: NICEATM announces availability of the ICCVAM Test Method
Evaluation Report: Validation Status of Five In Vitro Test Methods
Proposed for Assessing Potential Pyrogenicity of Pharmaceuticals and
Other Products (NIH Publication 08-6392). The test method evaluation
report (TMER) describes five in vitro pyrogen test methods that can be
used for detecting Gram-negative endotoxin in human parenteral
pharmaceuticals. The report includes ICCVAM's (a) Recommendations on
uses and limitations for each test method, (b) recommendations for
standardized protocols, (c) recommendations for future studies, and (d)
recommendations for the development of performance standards.
ICCVAM concludes that none of these test methods can be considered
as a complete replacement for the rabbit pyrogen test (RPT) for all
testing situations for the detection of Gram-negative endotoxin.
However, ICCVAM recommends that they can be considered for use on a
case-by-case basis to detect Gram-negative endotoxin in human
parenteral drugs, subject to product-specific validation to demonstrate
equivalence to the RPT, in accordance with applicable U.S. Food and
Drug Administration regulations. When used in this manner, these
methods can reduce the number of animals needed for pyrogenicity
testing. The report also recommends that these
[[Page 71004]]
and other in vitro alternative test methods be considered prior to in
vivo pyrogenicity testing, where determined appropriate for a specific
testing situation.
NICEATM also announces availability of the final ICCVAM Background
Review Document: Validation Status of Five In Vitro Test Methods
Proposed for Assessing Potential Pyrogenicity of Pharmaceuticals and
Other Products (NIH Publication 08-6391). The final background review
document (BRD) provides the data and analyses used to assess the
current validation status of these five in vitro test methods.
The ICCVAM TMER and supporting BRDs have been forwarded to U.S.
Federal agencies for regulatory and other acceptance consideration,
where applicable. Responses received will be posted on the NICEATM-
ICCVAM Web site.
ADDRESSES: Electronic copies of the ICCVAM TMER and final BRD are
available from the NICEATM-ICCVAM Web site at http://iccvam.niehs.nih.gov or by contacting NICEATM (see FOR FURTHER
INFORMATION CONTACT).
FOR FURTHER INFORMATION CONTACT: Dr. William S. Stokes, Director,
NICEATM, NIEHS, P.O. Box 12233, MD EC-17, Research Triangle Park, NC
27709, (telephone) 919-541-2384, (fax) 919-541-0947, (e-mail)
[email protected] Courier address: NICEATM, NIEHS, 79 T.W.
Alexander Drive, Building 4401, Room 3128, Research Triangle Park, NC
27709.
SUPPLEMENTARY INFORMATION:
Background
In 2005, the European Centre for the Validation of Alternative
Methods (ECVAM), a unit of the Institute for Health and Consumer
Protection at the European Commission's Joint Research Centre,
submitted BRDs for five in vitro pyrogen test methods proposed as
replacements for the RPT to ICCVAM for formal evaluation of their
scientific validity for regulatory testing purposes. ICCVAM unanimously
agreed that the five submitted in vitro pyrogen test methods should
have high priority for evaluation. On December 16, 2005, NICEATM
published a Federal Register notice (Vol. 70, No. 241, pages 74833-
74834), requesting public comments on the appropriateness and relative
priority of convening an independent peer review panel (Panel) to
evaluate the validation status of the five in vitro pyrogen test
methods, the nomination of scientists to serve on the Panel, and the
submission of data from in vivo and in vitro pyrogenicity testing.
Based on the ECVAM BRDs as well as data and information submitted in
response to the aforementioned Federal Register notice, NICEATM
subsequently compiled a comprehensive draft BRD on the five in vitro
pyrogen test methods and released it for public comment on December 12,
2006 (Vol. 71, No. 238, pages 74533-74534).
On February 6, 2007, NICEATM and ICCVAM convened a Panel to review
the ICCVAM draft BRD for errors and omissions and to evaluate the
validation status of the five in vitro pyrogen test methods. The Panel
also reviewed the extent that the information contained in the ICCVAM
draft BRD supported the ICCVAM draft test method recommendations for
proposed test method uses, standardized protocols, test method
performance standards, and additional studies. The Panel considered
public comments made at the Panel meeting, as well as public comments
submitted in advance of the meeting, before concluding their
deliberations. NICEATM made the Panel's report available in May 2007
(Vol. 72, No. 89, pages 26395-26396). The ICCVAM draft BRD and draft
recommendations, the Panel's report, and all public comments were made
available to the Scientific Advisory Committee on Alternative
Toxicological Methods (SACATM) for review and comment at their meeting
on June 12, 2007 (Vol. 72, No. 83, pages 23831-23832).
ICCVAM considered the Panel's report, all public comments, and the
comments of SACATM in finalizing its recommendations on the use of
these five in vitro test methods proposed for assessing potential
pyrogenicity of pharmaceuticals and other products. The ICCVAM TMER
includes the ICCVAM recommendations on uses and limitations for each
test method, standardized protocols, future studies, and the
development of performance standards, as well as the Panel's report and
Federal Register notices. The final BRD, which provides the supporting
documentation for this report, is available as a separate document.
ICCVAM forwarded the ICCVAM TMER and the supporting final BRD to U.S.
Federal agencies for consideration, in accordance with the ICCVAM
Authorization Act of 2000 (42 U.S.C. 285l-3). Agency responses to the
ICCVAM test method recommendations will be made available on the
NICEATM-ICCVAM Web site as they are received.
Background Information on ICCVAM, NICEATM, and SACATM
ICCVAM is an interagency committee composed of representatives from
15 Federal regulatory and research agencies that use, generate, or
disseminate toxicological information. ICCVAM conducts technical
evaluations of new, revised, and alternative methods with regulatory
applicability and promotes the scientific validation and regulatory
acceptance of toxicological test methods that more accurately assess
the safety and hazards of chemicals and products and that refine,
reduce, and replace animal use. The ICCVAM Authorization Act of 2000
established ICCVAM as a permanent interagency committee of the NIEHS
under NICEATM. NICEATM administers ICCVAM and provides scientific and
operational support for ICCVAM-related activities. NICEATM and ICCVAM
work collaboratively to evaluate new and improved test methods
applicable to the needs of U.S. Federal agencies. Additional
information about ICCVAM and NICEATM can be found at http://www.iccvam.niehs.nih.gov.
SACATM was established January 9, 2002 (Vol. 67, No. 49, page
11358), and is composed of scientists from the public and private
sectors. SACATM provides advice to the Director of the NIEHS, to
ICCVAM, and to NICEATM regarding the statutorily mandated duties of
ICCVAM and activities of NICEATM. Additional information about SACATM,
including the charter, roster, and records of past meetings, can be
found at http://ntp.niehs.nih.gov/go/167.
Dated: November 7, 2008.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences
and National Toxicology Program.
[FR Doc. E8-27790 Filed 11-21-08; 8:45 am]
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