Federal Register / Vol. 75, No. 89 / Monday, May 10, 2010 / Notices 25867 

Background 

ICCVAM originally recommended the 

LLNA as a valid stand-alone alternative 

method to existing ACD test methods in 

1999 (NIH publication No. 99–4494; 

available at http://iccvam.niehs.nih.gov/ 

docs/immunotox_docs/llna/ 

llnarep.pdf). ICCVAM recommended 

that the LLNA could be used as a 

substitute for the existing guinea pig 

based test methods for most testing 

situations, which would reduce the 

number of animals required and avoid 

pain and distress. The Environmental 

Protection Agency (EPA), the Food and 

Drug Administration (FDA), and the 

Consumer Product Safety Commission 

(CPSC) subsequently accepted the 

method as a valid substitute. The 

Organization for Economic Co-operation 

and Development (OECD) adopted the 

LLNA as international OECD Test 

Guideline 429 and the International 

Standards Organization (ISO) adopted 

the LLNA as ISO Test 10993–10. 

The updated LLNA test method 

protocol uses 20% fewer animals than 

the original LLNA protocol 

recommended by ICCVAM in 1999, and 

provides improved guidance on dose 

selection and other procedures to 

improve assay accuracy and 

reproducibility. The rLLNA procedure 

can further reduce the number of 

animals required by 40% compared to 

the updated LLNA protocol multi-dose 

procedure. ICCVAM recommends that 

the rLLNA test method should be 

routinely considered before conducting 

the traditional multi-dose LLNA, and 

should be used as the initial test for 

ACD where determined appropriate. 

ICCVAM evaluation and complete 

recommendations for the updated LLNA 

test method protocol and the rLLNA 

procedure are provided in the ICCVAM 

Test Method Evaluation Report: The 

Reduced Murine Local Lymph Node 

Assay: An Alternative Test Method 

Using Fewer Animals to Assess the 

Allergic Contact Dermatitis Potential of 

Chemicals and Products (NIH 

Publication No. 09–6439, available at 

http://iccvam.niehs.nih.gov/methods/ 

immunotox/LLNA–LD/TMER.htm). 

ICCVAM also recommends that the 

LLNA test method performance 

standards can be used to efficiently 

evaluate the validity of modified test 

methods that are mechanistically and 

functionally similar to the traditional 

LLNA. The LLNA test method 

performance standards are provided in 

the ICCVAM report, Recommended 

Performance Standards: Murine Local 

Lymph Node Assay (NIH Publication 

No. 09–7357, available at http:// 

iccvam.niehs.nih.gov/methods/ 

immunotox/PerfStds/llna-ps.htm). 

ICCVAM evaluated the updated 

versions of the LLNA in response to a 

2007 nomination from the CPSC 

(http://iccvam.niehs.nih.gov/methods/ 

immunotox/llnadocs/ 

CPSC_LLNA_nom.pdf). The nomination 

also requested that ICCVAM evaluate 

the validation status of (1) new versions 

of the LLNA test method protocol that 

do not require the use of radioactive 

materials; (2) use of the LLNA to test 

mixtures, aqueous solutions, metals, 

and other substances; and (3) use of the 

LLNA to determine ACD potency 

categories for hazard classification and 

labeling purposes. ICCVAM 

recommendations on these new versions 

and applications are undergoing 

finalization and will be forwarded to 

Federal agencies in 2010. 

Agency Reponses to ICCVAM 

Recommendations 

In September 2009, ICCVAM 

forwarded final test method 

recommendations for the rLLNA, the 

updated LLNA test method protocol, 

and LLNA performance standards to 

U.S. Federal agencies for consideration, 

in accordance with the ICCVAM 

Authorization Act of 2000 (42 U.S.C. 

285l–3(e)(4)) (74 FR 50212). The 

ICCVAM Authorization Act requires 

member agencies to review ICCVAM 

test method recommendations and 

notify ICCVAM in writing of their 

findings no later than 180 days after 

receipt of recommendations. The Act 

also requires ICCVAM to make ICCVAM 

recommendations and agency responses 

available to the public. Agency 

responses are to include identification 

of relevant test methods for which the 

ICCVAM test method recommendations 

may be added or substituted, and 

indicate any revisions or planned 

revisions to existing guidelines, 

guidances, or regulations to be made in 

response to these recommendations. 

Background Information on ICCVAM 

and NICEATM 

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 on their Web 

site (http://www.iccvam.niehs.nih.gov). 

Dated: April 30, 2010. 

John R. Bucher, 

Associate Director, National Toxicology 

Program. 

[FR Doc. 2010–10954 Filed 5–7–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Toxicology Program (NTP) 

Interagency Center for the Evaluation 

of Alternative Toxicological Methods 

(NICEATM): International Workshop on 

Alternative Methods To Reduce, 

Refine, and Replace the Use of 

Animals in Vaccine Potency and Safety 

Testing: State of the Science and 

Future Directions 

AGENCY: National Institute of 

Environmental Health Sciences 

(NIEHS), National Institutes of Health 

(NIH), Department of Health and Human 

Services. 

ACTION: Announcement of a workshop. 

SUMMARY: The Interagency Coordinating 

Committee on the Validation of 

Alternative Methods (ICCVAM) and 

NICEATM announce an upcoming 

‘‘International Workshop on Alternative 

Methods to Reduce, Refine, and Replace 

the Use of Animals in Vaccine Potency 

and Safety Testing: State of the Science 

and Future Directions.’’ The workshop 

will bring together an international 

group of scientific experts from 

government, industry, and academia to 

review the current state of the science, 

availability, and future need for 

alternative methods that can reduce, 

refine, and replace the use of animals 

for human and veterinary vaccine postlicensing potency and safety testing. 

Plenary and breakout sessions will 

address current U.S. and international 

regulatory requirements, currently 

available alternatives, and future 

research, development, and validation 

activities needed to further advance the 

use of alternative methods for vaccine 

post-licensing potency and safety 

testing. This workshop is free and open 


jlentini on DSKJ8SOYB1PROD with NOTICES
25868 Federal Register / Vol. 75, No. 89 / Monday, May 10, 2010 / Notices 

to the public with attendance limited 

only by the space available. Abstracts 

for scientific posters for display at the 

workshop are also invited (see 

SUPPLEMENTARY INFORMATION). 

DATES: The workshop will be held on 

September 14–16, 2010. Sessions will 

begin at 8:30 a.m. and end at 

approximately 5 p.m. on all days. The 

deadline for submission of poster 

abstracts is July 29, 2010. Individuals 

who plan to attend are asked to register 

in advance (by August 30, 2010) with 

NICEATM. 

ADDRESSES: The workshop will be held 

at the William H. Natcher Conference 

Center, 45 Center Drive, NIH Campus, 

Bethesda, MD 20892. Persons needing 

special assistance, such as sign language 

interpretation or other reasonable 

accommodation in order to attend, 

should contact 919–541–2475 voice, 

919–541–4644 TTY (text telephone), 

through the Federal TTY Relay System 

at 800–877–8339, or e-mail to 

niehsoeeo@niehs.nih.gov. Requests 

should be made at least 14 days in 

advance of the event. 

FOR FURTHER INFORMATION CONTACT: 

Correspondence should be sent by mail, 

fax, or e-mail to Dr. William S. Stokes, 

NICEATM Director, NIEHS, P.O. Box 

12233, MD K2–16, Research Triangle 

Park, NC 27709, (phone) 919–541–2384, 

(fax) 919–541–0947, (e-mail) 

niceatm@niehs.nih.gov. 

SUPPLEMENTARY INFORMATION: 

Background 

Vaccines represent a vital and costeffective tool in the prevention of 

infectious diseases in humans and 

animals. Regulatory authorities require 

post-licensing potency and safety testing 

of human and veterinary vaccines to 

ensure their effectiveness and minimize 

potential adverse health effects. Because 

some of these tests require large 

numbers of laboratory animals that may 

experience unrelieved pain and distress, 

the development and validation of 

alternative methods that can reduce, 

refine, and replace the use of animals 

for vaccine potency and safety testing is 

one of ICCVAM’s four highest priorities. 

The workshop goals are to (1) review the 

state of the science of alternative 

methods that are currently available 

and/or accepted for use that can reduce, 

refine (less pain and distress), and 

replace animal use in vaccine potency 

and safety testing, and discuss ways to 

promote their implementation; (2) 

identify knowledge and data gaps that 

should be addressed to develop 

alternative methods that can further 

reduce, refine, and/or replace the use of 

animals in vaccine potency and safety 

testing; and (3) identify and prioritize 

research, development, and validation 

efforts needed to address these 

knowledge and data gaps in order to 

advance alternative methods for vaccine 

potency and safety testing while 

ensuring the protection of human and 

animal health. 

Preliminary Workshop Agenda 

Day 1 Tuesday, September 14, 2010 

• Welcome and Introduction of 

Workshop Goals and Objectives 

• Overview of Public Health Needs 

and Regulatory Requirements for 

Vaccine Safety and Potency Testing 

• Replacement Methods for Vaccine 

Potency Testing: Current State of the 

Science 

• Breakout Groups: Non-animal 

Replacement Methods for Vaccine 

Potency Testing 

• Human Vaccines 

• Veterinary Vaccines 

Day 2 Wednesday, September 15, 2010 

• Refinement Alternatives: Using 

Serological Methods to Avoid Challenge 

Testing 

• Refinement Alternatives: Using 

Earlier Humane Endpoints to Avoid or 

Minimize Animal Pain and Distress in 

Vaccine Potency Challenge Testing 

• Reduction Alternatives: Strategies 

to Further Reduce Animal Numbers for 

Vaccine Potency Testing 

• Breakout Groups: Refinement and 

Reduction of Animal Use for Vaccine 

Potency Testing 

• Human Vaccines 

• Veterinary Vaccines 

Day 3 Thursday, September 16, 2010 

• Vaccine Post-licensing Safety 

Testing: Reduction, Refinement and 

Replacement Methods and Strategies 

• Breakout Groups: Post-license 

Vaccine Safety Testing: Alternative 

Strategies for the Replacement, 

Refinement, and Reduction of Animals 

• Human Vaccines 

• Veterinary Vaccines 

• Closing Comments 

Registration 

Registration information, tentative 

agenda, and additional meeting 

information are available on the 

workshop Web site (http:// 

iccvam.niehs.nih.gov/meetings/ 

BiologicsWksp-2010/ 

BiologicsWksp.htm) and upon request 

from NICEATM (see FOR FURTHER

INFORMATION CONTACT). 

Call for Abstracts 

ICCVAM and NICEATM invite the 

submission of abstracts for scientific 

posters to be displayed during this 

workshop. Posters should address 

current research, development, 

validation, and/or regulatory acceptance 

of alternative methods that may reduce, 

refine, and/or replace the use of animals 

in vaccine potency or vaccine postlicensing safety testing. The body of the 

abstract must be limited to 400 words or 

fewer. Key references relevant to the 

abstract may be included after the 

abstract body. However, the length of 

the abstract and references should not 

exceed one page. All submissions 

should be at least 12-point font and all 

margins for the document should be no 

less than one inch. Title information 

should include names of all authors and 

associated institutions. The name and 

contact information (i.e., address, phone 

number, fax number, e-mail address) for 

the corresponding or senior author 

should be provided at the end of the 

abstract. 

A statement indicating whether 

animals or humans were used in studies 

described in the poster must accompany 

all abstracts. All abstracts that involve 

studies using animals or animal tissues 

should be accompanied by a statement 

by the senior author certifying that all 

animal use was carried out in 

accordance with applicable laws, 

regulations, and guidelines, and that the 

studies were approved by the 

appropriate Institutional Animal Care 

and Use Committee or equivalent. A 

statement that all human studies were 

conducted in accordance with 

applicable laws, regulations, and 

guidelines, and that the studies were 

approved by the appropriate 

Institutional Review Board or equivalent 

must accompany any abstracts that 

involve studies using humans. 

Abstracts must be submitted by e-mail 

to niceatm@niehs.nih.gov. The deadline 

for abstract submission is close of 

business on July 29, 2010. ICCVAM and 

NICEATM will review the submitted 

abstracts. The corresponding author will 

be notified of the abstract’s acceptance 

approximately five weeks prior to the 

workshop. Guidelines for poster 

presentations will be sent to 

corresponding authors along with the 

notification of acceptance. 

Background Information on ICCVAM 

and NICEATM 

ICCVAM is an interagency committee 

composed of representatives from 15 

U.S. Federal regulatory and research 

agencies that require, use, or generate 

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 


jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 75, No. 89 / Monday, May 10, 2010 / Notices 25869 

that more accurately assess the safety 

and health hazards of chemicals and 

products and that refine (less pain and 

distress), reduce, or replace animal use. 

The ICCVAM Authorization Act of 2000 

(42 U.S.C. 2851–2, 2851–5 [2000]), 

available at http://iccvam.niehs.nih.gov/ 

about/PL106545.htm) established 

ICCVAM as a permanent interagency 

committee of the NIEHS under 

NICEATM. NICEATM administers 

ICCVAM, provides scientific and 

operational support for ICCVAM-related 

activities, and coordinates international 

validation studies. 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, guidelines for nomination of 

test methods for validation studies, and 

guidelines for submission of test 

methods for ICCVAM evaluation are 

available at http://iccvam.niehs.nih.gov. 

Dated: April 30, 2010. 

John R. Bucher, 

Associate Director, National Toxicology 

Program. 

[FR Doc. 2010–10958 Filed 5–7–10; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2010–N–0233] 

The National Institutes of Health and 

the Food and Drug Administration 

Joint Leadership Council: 

Stakeholders Meeting; Request for 

Comments 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice of public meeting; 

request for comments. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing a 

public meeting, in conjunction with the 

National Institutes of Health (NIH), to 

solicit comments from interested 

persons on how the agencies can more 

effectively collaborate to advance the 

translation of biomedical research 

discoveries into approved diagnostics 

and therapies as well as promote 

science to enhance the evaluation tools 

used for regulatory review. A newly 

formed NIH–FDA Joint Leadership 

Council will help ensure that regulatory 

considerations form an increasing 

component of biomedical research 

planning, and that the latest science is 

integrated into the regulatory review 

process. 

DATES: The public meeting will be held 

on June 2, 2010, from 8:30 a.m. to 12:30 

p.m. Persons interested in attending the 

meeting must register by Wednesday, 

May 26, 2010, at 5 p.m. e.s.t. (see 

section III of this document). Submit 

written or electronic comments by 

Wednesday, May 26, 2010, at 5 p.m. 

e.s.t. 

ADDRESSES: The public meeting will be 

held at FDA, 10903 New Hampshire 

Ave., Bldg. 31, rm. 1503C, Silver Spring, 

MD 20993–0002. 

Submit written comments to the 

Division of Dockets Management (HFA– 

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. Submit electronic comments 

to http://www.regulations.gov. All 

comments should be identified with the 

docket number found in brackets at the 

heading of this document. 

FOR FURTHER INFORMATION CONTACT: 

Rakesh Raghuwanshi, Office of the 

Commissioner, Food and Drug 

Administration, 10903 New Hampshire 

Ave., Bldg. 32, rm. 4283, Silver Spring, 

MD 20993–0002, 301–796–4769, FAX: 

301–847–8617, e-mail: 

rakesh.raghuwanshi@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

With the dramatic breakthroughs 

occurring in biomedical research 

discovery, new public health challenges 

on the rise, an ever-changing economic 

landscape resulting from globalization, 

and the prospect for fundamental 

changes to healthcare delivery in the 

United States, there is a pressing need 

for greater collaboration between FDA 

and NIH. Both NIH and FDA have the 

goals of translating science discoveries 

into medical products and therapies, 

and both NIH and FDA have important 

roles and contributions to make towards 

these efforts. To address these important 

areas of common interest, NIH and FDA 

announced a new partnership effort that 

includes, among other initiatives, the 

regulatory science program and the 

NIH–FDA Joint Leadership Council. 

The NIH–FDA Joint Leadership 

Council provides a forum for the 

leadership of both agencies to: (1) Work 

together on strategic planning at a high 

level; (2) stimulate an enhanced culture 

of collaboration between the agencies at 

all levels; and (3) further coordinate and 

target efforts to promote promising new 

therapies using the latest technological 

advances, such as stem cell biology, 

biomarkers, and computational 

sciences. NIH and FDA plan to work 

jointly to address the gap between 

biomedical research discoveries and 

new medical products. They can create 

new programs to support development 

of innovative therapies and promote 

personalized medicine, utilizing new 

clinical trial design strategies and 

regulatory review processes 

incorporating the use of genetic or other 

biomarkers and information 

technologies. These activities will also 

support postmarketing and/or other 

population-based surveys for safety 

assessments. Overall, there are many 

new avenues for NIH and FDA to 

explore such that we can deliver safer 

and more effective treatments faster. 

II. Scope of the Meeting 

FDA and NIH are interested in 

receiving comments from the public on 

the regulatory considerations that 

should be an integral part of the 

biomedical research program 

development and scientific tools or 

approaches that would enhance the 

ability to evaluate new medical 

products. The comments should focus 

on ways in which NIH and FDA can 

partner to promote interdisciplinary 

biomedical research through scientific 

exchange and new programs designed to 

advance innovation and development of 

new therapies incorporating many of the 

latest basic research discoveries. 

Suggestions about the ways FDA and 

NIH can work together to promote an 

integrated biomedical research agenda 

including regulatory review approaches 

and/or processes on areas of common 

interest and mission are being sought. 

Some areas for which we are 

specifically interested in input are the 

following: 

1. What steps should be taken to 

enhance the translation of biomedical 

research discoveries into new and 

approved preventatives, diagnostics, 

therapies, or devices for clinical use? 

2. What are the priority scientific 

issues that currently need to be 

addressed (e.g., clinical trial design, 

endpoint selection and qualification, 

bioinformatics needs) in order to inform 

regulatory assessments and analyses of 

new products? 

3. How could we enhance the 

exchange of scientific information 

across all sectors in order to better 

identify and prioritize scientific areas 

for emphasis in regulatory research? 

4. What mechanisms for the support 

of regulatory science research would be 

most effective and efficient in 

addressing pressing priority areas in the 

translational pipeline? 

III. Registration To Attend and/or To 

Participate in the Meeting 

If you wish to attend the public 

meeting, you must register by e-mailing 

Rakesh Raghuwanshi 


jlentini on DSKJ8SOYB1PROD with NOTICES