Science Advisory Board Meeting
(August 29-30, 2006)
August 29, 2006:
The meeting was called to order by the Chair of the Science
Advisory Board (SAB), Dr. Daniel Acosta, Jr., Ph.D.,
Michael Aschner, Ph.D., Professor, Department of Pediatrics,
· Dr. James S. Bus, Ph.D., DABT, Director of External Technology, Toxicology and Environmental Research & Consulting, The Dow Chemical Company
Gillett, DVM, Ph.D., Sr. Vice President, Sierra Biomedical,
· Dr. Timothy P. Pastoor, Ph.D., DABT, Head, NAFTA Human Safety Department, Syngenta Crop Protection Inc.
· Dr. Anthony L. Pometto, Ph.D., Professor, Department of Food Science & Human Nutrition, Iowa State University
· Dr. James A. Popp, DVM, Ph.D., Co-founder and Co-owner, Stratoxon LLC
Stephen M. Roberts, Ph.D., Professor and Director,
Also present were representatives from the FDA Science Advisory Board, FDA liaisons to the NCTR SAB and the various divisions/offices of NCTR including:
· Dr. Bob Buchanan, CFSAN
· Dr. Kevin Greenlees, CVM
· Dr. Joe Hanig, CDER
· Dr. Lily Jung, Consumer Representative
· Dr. Ron Lorentzen, CFSAN
· Dr. Shirley Murphy, CDER
· Dr. Paul Norris, ORA
· Dr. Xavier Pi-Sunyer, FDA Science Board
· Dr. Leonard Schechtman, NCTR’s Designated Executive Secretariat
· Dr. John Thomas, FDA Science Board
· Dr. Kathleen Uhl, OWH
· Dr. Tom Wells, UAMS
Dr. Schechtman read a statement for the record to confirm that no NCTR Science Advisory Board members had any financial or other conflicts of interest with any of the topics listed in the meeting agenda. All participants were given the opportunity to comment and were instructed to preclude themselves from further participation if the discussions turned to any topics that would be considered a conflict of interest.
Dr. Acosta welcomed two members of the FDA Science Board, Dr. Pi-Sunyer and Dr. Thomas, who will provide feedback regarding the SAB meeting to the Board and the Commissioner. Both FDA Science Board members expressed their thanks for the opportunity to participate in the meeting.
Dr. Slikker, Acting Director of NCTR, presented an update on the Center. He spoke about the recent renovations to the NCTR campus, the 35-year anniversary of NCTR, a brief history of NCTR, the composition of NCTR’s staff, and the Center’s unique role within FDA’s regulatory environment. He noted that NCTR’s mission is to conduct peer-reviewed scientific research and to provide information vital to the FDA’s ability to make sound scientific decisions on regulatory issues.
Dr. Slikker noted that NCTR’s goal is to translate basic research data (such as that generated by the NIH) into regulatory tools for the FDA. He discussed examples of NCTR’s research that support the Center’s strategic priorities of:
1. Critical Path to Personalized Nutrition and Medicine
· Voluntary Genomics Data Submission (VGDS)
· Microarray Quality Control Project (MAQC)
· ArrayTrack (a bioinformatics tool)
2. Translational and Applied Toxicology
· Alpha beta hydroxy acids and tattoo ink studies conducted at the NIEHS/FDA Center for Phototoxicology at NCTR
· Ketamine (an anesthetic agent) pediatric studies
3. Food Defense and Food Safety
· Rapid identification methods of foodborne pathogens
· Food residues and antibiotic resistance
· Acrylamide (development in fried foods)
4. Standards Development of Biomarkers for Regulated Products
· Micronucleus assay
· Cognitive function assessment
Dr. Slikker discussed NCTR’s appropriated resources and the various funding challenges NCTR has experienced. Dr. Slikker stated that from 2000 to 2006, NCTR’s appropriated resources increased slightly and that the 2007 projected budget would result in a devastating downturn in funding. However, between the Senate’s proposal and the House’s proposal, the Senate’s budget proposal is the most beneficial to NCTR. The steps NCTR is taking in anticipation of the 2007 budget shortfall include:
· Conserving resources (approximately 30 individuals took early retirement)
· Improving efficiency (more efficient ways to run the facility such as reducing energy consumption and movement to energy-efficient buildings)
· Seeking collaboration opportunities within the FDA and with other government agencies
· Seeking additional funding from FDA
· Working with USDA (as a liaison) to encourage collaboration between NCTR and the Department of Homeland Security
Dr. Pastoor requested that Dr. Slikker explain how the budget is built and appropriated. Dr. Slikker provided a brief explanation of the multi-year process which involves projections provided by HHS to NCTR as a result of the President’s proposed budget, proposals from NCTR, and eventual approval of the budget by Congress.
Dr. Acosta then directed the discussion towards the overview of the different Centers within the FDA. Dr. Shirley Murphy and Dr. Joe Hanig represented CDER; Dr. Daniel Schultz represented CDRH, Dr. Robert Buchanan from CFSAN, Dr. Kevin Greenless from CVM, Dr. Paul Norris from ORA and Dr. Kathleen Uhl from OWH. Each representative briefly described the activities and mission of their respective Center. Additionally, they each discussed the significant role that NCTR plays in helping their Center achieve the mission of the organization through successful research collaborations with NCTR.
Dr. Bus asked how often NCTR resources get used for basic testing of chemicals or drugs of interest within the framework of an IAG, in the same way that Centers collaborate with NTP. Dr. Lorentzen addressed the question by describing several research successes in which NCTR played a role. Dr. Buchanan added to the response by stating that NCTR’s budget would not be able to solely fund the toxicological studies that are conducted.
Dr. Pastoor asked Dr. Buchanan for an explanation of risk assessment, i.e. what it really means in a practical context, and also asked about FDA’s role in genetically modified foods. Dr. Buchanan said that any major regulation issued by FDA must now be accompanied by a risk assessment. He stated that CFSAN relies heavily on NCTR to provide the toxicological data and that NCTR and others have also worked on expanding the risk assessment techniques and their applications. Dr. Buchanan’s also responded that genetically modified foods is a matter of Federal jurisdictions – the lawyers have the option of assigning each category of food to either the EPA, the USDA, or the FDA depending on the point at which the modified characteristic is introduced into the product.
The meeting was suspended at 10:45 a.m. for a short break and reconvened at 11:00 a.m.
After the break, Dr. Bill Allaben – Associate Director for Scientific Coordination, NCTR and the FDA liaison to the NTP – spoke to the members of the board regarding the history of the NTP, its structure, and the partnership between NCTR and NTP. He explained that the driving forces in the IAG between NCTR/FDA and NTP/NIEHS were to make sure the FDA regulators 1) were involved during the design phase of the studies, and 2) had the best possible information at the end of the study to make a risk-management decision. In summary, Dr. Allaben informed the attendees that over the last six years the FDA has averaged approximately $13 million a year from the NTP to support FDA research using FDA scientists.
The Board next heard presentations from each of the research divisions within NCTR:
· Division of Biochemical Toxicology – Dr. Fred Beland
· Division of Neurotoxicology – Dr. Merle Paule
· Division of Genetic and Reproductive Toxicology – Dr. Martha Moore
· Division of Systems Toxicology – Dr. Yvonne Dragan
· Division of Epidemiology and Pharmacogenomics – Dr. Luke Ratnasinghe
· Division of Biometry and Risk Assessment –Dr. Ralph Kodell
· Division of Veterinary Services – Dr. Jeff Carraway
· Division of Microbiology – Dr. Cerniglia
The meeting was suspended at 12:30 p.m. for lunch and reconvened
at approximately 1:00 p.m.
After lunch, Dr. Acosta opened the meeting for questions.
Dr. Murphy from CDER corrected a statement she made earlier that methylphenidate (Ritalin) has been deemed safe. In reality, she clarified, NIH has determined that more extensive research needs to be done in this area and has awarded NCTR several million dollars to continue this research.
Dr. John Thomas, FDA Science Board member, requested that the Centers be more generous about sharing and adopting successful methods that have been developed across the FDA or by industry. Dr. Buchanan reinforced this request and stressed the importance of method validation and the transfer of knowledge and technology so that the method can be applied in the field laboratories.
Dr. Roberts asked the Center representatives for examples of toxicological-related problems with which NCTR was not able to help. Dr. Murphy, Dr. Lorentzen, and Dr. Uhl all agreed that given enough resources, NCTR is quite capable of handling toxicological-related issues. Dr. Lorentzen provided the example of using NTP resources to build the phototoxicology center at NCTR so that research could be conducted in this area. Dr. Uhl also commented that there is a lack of research in the area of reproductive toxicology in humans not only at NCTR, but in the entire scientific community. Later in the meeting, Dr. Hanig came back to this question and added that he would like to see the research approval and prioritization process reevaluated.
Dr. Buchanan asked if NCTR has an active program in place to find alternatives to large animal studies. Dr. Schechtman described an interagency coordinating committee whose purpose is to validate alternative methods. Dr. Slikker mentioned the promise of imaging as an alternative and appealed to CDRH representatives to jointly participate with NCTR, in collaboration with Arkansas Children’s Hospital and UAMS, in utilizing imaging technology. Dr. Schultz from CDRH agreed that they have the expertise to participate in that type of research effort with NCTR.
Dr. Popp asked for an explanation of the term “biomarker” and an update on how global perspectives on the topic are being integrated. A discussion between the board members revealed that the term “biomarker” is used in various contexts and needs to be better defined. Dr. Acosta suggested the topic be more thoroughly discussed in a future meeting.
Dr. Paule from NCTR presented the Neurotoxicology Division’s response to the report from the SAB’s Subcommittee on Neurotoxicology that was issued in January 2004. He discussed 1) the division’s ongoing research efforts, 2) the increased scientific guidance being provided to the scientists, 3) the effects of decreased funding on the division, 4) the increased external collaborations and more focused research efforts, and 5) the emphasis being placed on database development. Dr. Gillett expressed frustration with the 2.5 year delay between the review and the response. It was later acknowledged that the delay was due to decreased funding.
In response to Dr. Acosta’s question to Dr. Paule about how the scientists’ success is gauged, Dr. Paule described NCTR’s peer-review process. Following Dr. Paule’s explanation, there was discussion among the Board members about the benefits of possibly decreasing the frequency of the reviews and increasing the amount of mentoring.
Members of the committee agreed that one or two division reviews would be conducted each year, i.e. each division will be reviewed every four to five years. The Microbiology Division was identified as the next possible review to take place.
The meeting concluded and the SAB members and guests toured
the NCTR/Jefferson Labs.
Science Advisory Board Meeting
(August 29-30, 2006)
August 30, 2006:
The meeting was called to order by the Chair of the Science Advisory Board (SAB), Dr. Daniel Acosta.
Dr. Leonard Schechtman stated that the open portion of the meeting would conclude at 10:00 a.m., followed at 10:30 a.m. by a closed executive session of the SAB members only.
Dr. Slikker thanked everyone involved in the organization of events both prior to and during the meeting and then gave a presentation on NCTR’s strategic focus and recent realignment. He explained that NCTR is realigning its research and resources into areas directly responding to agency regulatory issues. NCTR’s expanded technical innovation is vital to speed FDA-regulated product review and safety assessments.
The possible approaches to prioritize research at NCTR include 1) product-selection boards, 2) requests-for-proposals, 3) research initiated by regulators, and 4) research initiated by the researchers themselves. Of these four approaches, Dr. Slikker noted that the regulator-initiated and the researcher-initiated approaches have the greatest opportunity for improving the research prioritizing process.
· To improve the regulator-initiated approach, he proposed the creation of a new position for NCTR – Associate Director for Regulatory Activities. The person in this position would serve as a liaison between NCTR and the other Centers, identifying regulatory groups that need additional research support and educating them about NCTR’s capabilities to provide that support.
· To improve the researcher-initiated approach, he proposed the realignment of some of the NCTR divisions to be more focused on the regulatory responsibility of the FDA. This realignment would use NCTR’s strategic plan, cross-linked to the FDA’s strategic plan as a guide. Dr. Slikker stated that the NCTR and FDA strategic plans are evergreen documents that will be revised in a concordant manner.
Dr. Slikker proposed the realignment of resources and expertise from the Division of Biometry and Risk Assessment and the Division of Molecular Epidemiology to create a new Division of Personalized Nutrition and Medicine that directly supports and anticipates FDA research and regulatory needs in this area. The three primary reasons he is moving in the direction of personalized medicine are:
1. Subpopulations can now be identified down to the individuals that are more receptive to certain drug therapies, and individuals that may have adverse effects.
2. The proteomic, metabolomic and genomic data gathered via ‘omics’ technologies together with other information available about the subpopulations should allow for speedier clinical trials.
3. Avoiding futile treatments on subpopulations will help to reduce the cost of health care.
He said that NCTR has a lot of interaction with the academic area, with industry through CRADAs, and with other government agencies through interagency agreements. NCTR’s key collaborations are with NTP/NIEHS, NICHD, EPA, NCI, USDA,
and NIDA. Dr. Slikker stated that he would like to diversify NCTR’s portfolio of partners. He also expressed a desire that this interaction continue to be improved within the rest of FDA; and encouraged the other Centers to pursue CRADA opportunities and form alliances in conjunction with NCTR.
Dr. Hanig and Dr. Lorentzen questioned Dr. Slikker about the amount of direct control NCTR has over the Center’s research programs. In response, Dr. Slikker agreed that NCTR can align some of its research more effectively to increase the interaction between the Center and the rest of the FDA. However, he also stressed that NCTR requires base funding in order to maintain operations, and that any funds from external sources should only supplement the base funding.
Dr. Thomas suggested to Dr. Slikker that instead of creating a new position for NCTR called Associate Director for Regulatory Activities, a better title might be something like Associate Director for External Scientific Affairs. He felt that other government agencies outside of the FDA would be more inclined to deal with NCTR if the term “regulatory activities” was not used because the agency considering the collaboration may not deal with any regulatory activities (i.e. NIH).
Dr. Kodell added to Dr. Hanig, Dr. Lorentzen, and Dr. Thomas’ earlier comments by saying that NCTR needs to be a more critical entity in the FDA. Although NCTR has made many contributions over the years, the FDA still sees NCTR as being different from the other regulatory centers; that NCTR does not have a regulatory mission. For this reason, Dr. Kodell agrees with the title proposed by Dr. Slikker which includes the word “regulatory.” Between the creation of this new “regulatory” position and emphasizing a research area that is high on the Agency’s priority list, Dr. Kodell expressed his support for Dr. Slikker’s reorganization plan. Dr. Buchanan then clarified with Dr. Slikker that this reorganization plan is not yet approved for public dissemination.
Dr. Buchanan opened a discussion regarding the use of the word “nutrition” in the newly proposed division’s name. He advised Dr. Slikker on the importance of getting buy-in from the nutrition community, including CFSAN, before making a final decision on the division name.
Dr. Pi-Sunyer asked Dr. Slikker to clarify his ideas on
molecular epidemiology and how involved he sees NCTR becoming with clinical
trials, the use of omics and imaging, and the use of existing data sets. In response, Dr. Slikker discussed NCTR’s
involvement with the CPAP Institute, CDISK and the other
Many of the board members stressed to Dr. Slikker the importance of keeping the CDC and other agencies involved and informed if NCTR gets involved with molecular epidemiology in a regulatory way. Dr. Buchanan especially was concerned about NCTR establishing a large infrastructure around an adverse reporting system.
The meeting was suspended for a five minute break.
Dr. Acosta then moved onto the next item of discussion; the site-visit reviews of the NCTR divisions. He described that periodically (every 4 years), two members of the SAB will conduct a peer review of the science of an individual division and the SAB would meet every 12 to 18 months with a concerted effort to stay on schedule.
Dr. Slikker announced that the Division of Microbiology will be the next division to be reviewed. He gave a brief description of the how the division is selected, the responsibilities of the division being reviewed, and what is expected of the SAB.
Dr. Beland questioned the need for a site review of the Division of Biochemical Toxicology if NCTR does not receive the resources it needs to perform research. Dr. Gillett stated that she believes the reviews are still worthwhile under these circumstances to understand and evaluate the direction of the science and how it relates to NCTR’s mission. Dr. Acosta added that critical analysis of research programs is even more important with limited resources in order to set research priorities. In addition, there was some discussion among the board and NCTR staff regarding the possible need for a reduction in force at NCTR if funds are not provided.
Dr. Buchanan expressed the importance of the SAB’s oversight to ensure that research being conducted at NCTR is in keeping with the FDA’s overall mission. He also stated that there should be boundaries established within which the PIs must operate when seeking external funds to ensure that the externally funded research is appropriate to the mission. Dr. Slikker responded by describing the protocol review process that requires review at multiple levels including input from other FDA Center/ORA scientists. All research proposals must go through this review process before resources are provided and must be focused on protecting public health and the mission of FDA.
In closing, Dr. Acosta stated for the record, with the board’s concurrence, that the dedication and the efforts of NCTR scientists are commendable and that they are meeting the mission of the FDA. They encourage careful review and analysis of NCTR’s mission and feel NCTR’s budget should reflect that mission. If there are budget cuts made, a thorough analysis of how those cuts affect the overall mission and activities of NCTR is needed.
The committee agreed that Dr. Acosta would draft a letter for the SAB members to review, indicating how pleased they are with the progress and the exciting new developments that are occurring at NCTR. After review and approval by the SAB members, the letter will be sent to Dr. Slikker and a copy sent to the Commissioner.
On behalf of NCTR, Dr. Leonard Schechtman and Dr. Bill Slikker thanked the exiting NCTR SAB members whose terms expire in June 2007 – Drs. Nancy Gillett and Dan Acosta (SAB Chair). They have served the NCTR/FDA admirably and were thanked for their many contributions during their tenure on the Board.
Dr. Acosta then thanked everyone for their participation and officially adjourned the meeting.
The public portion of the meeting concluded and the executive session began at approximately 10:30 a.m. after a short break.