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Fiscal Year 2008 (HTML version)

CVM Annual Report Fiscal Year 2008: October 1, 2007-September 30, 2008
 

pdf version

Contents

Some Highlights from Fiscal Year 2008

A Year of Recognition for the People of CVM
Animal Health Literacy Campaign

Animal Drug User Fee Program

Guidance for Genetically Engineered Animals

The Critical Path to Improved Public Health

BSE Feed Rule Enforcement: A Decade of Success

A Message from the Director

A Message from the Center Leadership Team


About CVM

Our Mission and Guiding Principles
Our Strategic Plan

Our Organization and Responsibilities

Our Sphere of Influence

Our Stakeholders and Partners


FY 2008 Challenges and Accomplishments

Accomplishing Department and Agency Objectives
Increasing the Availability of Safe and Effective Animal Drugs

Protecting the Health of Companion Animals

Increasing Drug Availability for Aquaculture and Other Minor Uses/Minor Species

Reducing Risk from Antimicrobial Resistance

Controlling Risk from BSE

Avoiding Unsafe Drug Residues in Human Food

Ensuring Feed Safety

Protecting Against Bioterrorism

Ensuring the Safety of Animal Clones and Genetically Engineered Animals

Additional Surveillance and Compliance Actions to Protect Public and Animal Health

Enhancing Productivity Through Achievement of Leadership and Management Objectives

Leveraging Productivity Through Partnerships
Communicating with Stakeholders

Appendices

A: Significant Regulations, Guidances, and Other Documents
B: Significant New Animal Drug Approvals

C: Awards
D: Publications

E: Budget and Staffing

F: Performance Goals


Some Highlights from Fiscal Year 2008


A Year of Recognition for the People of CVM

This year, as a theme for our Annual Report, we honor the achievements of our talented staff in the Center for Veterinary Medicine. It was an exceptional year for recognition – by agencies and organizations outside CVM – of our staff’s accomplishments.

Particularly noteworthy was the presentation of the “Legislator of the Year Award” to CVM’s Director Dr. Bernadette Dunham, who accepted the award on behalf of the Center. The award was presented by BIO, the biotechnology trade association, which paid tribute to all of those individuals who were responsible for development and public release of the animal cloning risk assessment.

Individual recognition came in several venues. For example, the Director of CVM’s Office of Management, David E. Wardrop, Jr., was presented the Department of Health and Human Services Award for Excellence in Management. This award is the third highest award granted by the Department of Health and Human Services and is conferred by the Secretary. The award acknowledges employees for contributing to the improvement of their Agency’s performance, which resulted in high productivity, efficiency, operation effectiveness, creative problem-solving, and reinforcing collaboration across the Department of Health and Human Services and/or another federal agency. The activity cited by the award: “For extraordinary contributions promoting and advancing the strategic goals of FDA/HHS through operational effectiveness, creative problem-solving, expert management processes, and collaborative leadership efforts.”

In addition, Office of Research scientist Dr. Renate Reimschuessel was one of 29 “Service to America Medal” finalists for medals awarded by the Partnership for Public Service, nominated for her discovery of the toxic properties of melamine in pet food. Dr. Burt Pritchett, one of our Office of Surveillance and Compliance BSE experts, was part of the “BSE Risk Status Dossier Team” that earned an award from the Secretary of Agriculture. The recognition was for work in achieving “controlled risk” status for the United States, as established by the World Organization for Animal Health.

Others merited recognition because their selection for important roles in the work of international bodies. Dr. David White of the Office of Research was selected to lead the writing of a key report for the Codex Alimentarius Commission’s ad hoc Intergovernmental Task Force on Antimicrobial Resistance, a report that is expected to provide internationally recognized guidance. Dr. Larisa Rudenko, CVM’s Senior Advisor for Biotechnology, during FY 2008 served as the first American on the European Food Safety Authority’s working group on animal cloning. An Office of Surveillance and Compliance staff member, Dr. Dragan Momcilovic, was selected as a member of the Scientific Committee for the Third International Feed Safety Conference. Dr. Marilyn Martinez Pelsor received an FDA Leveraging/Collaboration Award for her leadership in collaborations with scientists around the world.

Others on our staff received awards for work in solving significant public health problems. Drs. William Burkholder and Randall Lovell received FDA Excellence in Review Science awards for work related to melamine-contaminated pet food. Also seven members of CVM’s scientific staff – the Tissue Method Development and Implementation Working Group – received an FDA Group Recognition Award for outstanding intercenter scientific collaboration.

And there were more. Office of Research scientist Dr. Shaohua Zhao was awarded the 2008 FDA Scientific Achievement Award for “exceptional and outstanding contributions to protecting public health through CVM’s food safety surveillance, research and training programs.” Dr. Barry Hooberman received a Group Recognition Award for his contribution to the Interagency Risk Assessment Consortium Group. Several staff members earned FDA Group Recognition Awards for their work on the FDA Import Safety Working Group. Still others were recognized for their work related to new animal drug approvals, including staff members who were part of the FDA User Fee Negotiation Team, and those who were members of the Pre-Approval Inspection Decision Support System Working Group.

By highlighting a few award recipients, we do not intend to minimize the accomplishments of others who received recognition. You will find other individual and group honors documented in the pages of this report, especially in Appendix C. And we must acknowledge that the individual and group achievements that we highlight could not have occurred without the work of others in the Center and, in many instances, without the collaborative efforts of people outside the Center.

KEY STAFF PROMOTIONS

Appointments of individuals to serve in key positions are essential to the success of any organization.

Key promotions and assignments during FY 2008 were:

In the Office of New Animal Drug Evaluation –
Dr. David Newkirk was named Deputy Director for Administration; Dr. Karen Ekelman was named Director, Division of Human Food Safety; Dr. Dennis Bensley was named Director, Division of Manufacturing Technologies; and Dr. Linda Wilmot was named Director, Division of Production Drugs.

In the Office of Surveillance and Compliance – Dr. Martine Hartogensis was named Deputy Director.

In the Office of Research – Dr. David White was named Acting Director (and became Director in FY 2009); and Dr. Patrick McDermott was named Acting Director, Division of Animal and Food Microbiology.

In the Office of Minor Use and Minor Species Animal Drug Development – Dr. Meg Oeller was named Director.

Animal Health Literacy Campaign

During FY 2008, the Center initiated the Animal Health Literacy Campaign, based on the premise that increasing the knowledge of all those who are affected by animal health issues will help CVM accomplish its mission to the benefit of the public health.

The Animal Health Literacy Campaign began as an internal CVM outreach program through which the Communications staff would partner with the various CVM program offices to create and produce informational materials for various stakeholders, with an emphasis on educating consumers. The initial goal is to establish an ongoing, proactive program to educate our stakeholders on current animal health issues and human health issues that are related to animals and animal products. Included in this goal is informing the stakeholders of the range of useful information for which CVM is a source, thereby showcasing CVM’s animal health-related accomplishments on behalf of the public health. In addition to consumers, our stakeholders include pet owners, producers of food animals and their products, veterinarians, industry firms, and Federal and State agencies.

The immediate catalyst for the program was the success of a brochure for pet owners, Treating Pain in Your Dog: Keeping Your Best Friend Active, Safe and Pain Free1,that we published in 2007. The brochure provides information about the use of non-steroidal anti-inflammatory drugs and has been widely distributed to pet owners through veterinary practitioners (more than 50,000 copies have been ordered in bulk) and ordered by individuals (10,000 copies). The success of this brochure led staff members from several offices in CVM to suggest that the effort be continued and expanded.

The program dovetails with the health literacy initiative of the Department of Health and Human Services. The Department goal is to improve the ability of an individual to access, understand, and use health-related information and services to make appropriate health decisions. Other FDA Centers have joined in the campaign for improved health literacy.

We plan to use brochures and other handout materials, Internet resources (including an Animal Health Literacy Campaign Web page) and in-person outreach meetings to accomplish the goals of the initial phase. An example of written material is a recently released brochure on the Animal Feed Safety System; we sent more than 5,000 copies to State feed regulatory officials in August and September 2008. Copies can be requested through CVM’s Home Page or by calling the Communications staff at (240) 276-9300.

As the fiscal year ended, our staff had produced the following:

  • New informational materials such as posters, brochures, handouts, and even children’s schoolbook covers to offer safety information about subjects that include aquaculture drugs and doses and Salmonella infection from pet turtles.
  • An outreach program for veterinary technicians on the safe and effective use of non-steroidal anti-inflammatory drugs in companion animals.

This presentation, which has been made to a class of veterinary technician students, will be placed on the Veterinary Information Network in order to reach an international audience.

    • An outreach to veterinary technicians that includes explaining CVM’s role in drug approvals, how the technician can help ensure the safe and effective use of drugs, the importance of Client Information Sheets, and the reporting of adverse reactions.
    • A companion animal labeling outreach program to veterinary students stressing the importance of reading drug labels, explaining the kind of information that is available on drug labels, and similar topics.
    • Outreach to fish farmers, aquatic veterinarians, and fish hatchery managers to provide information on recently approved drugs for use in fish.
    • Outreach to aquatic veterinarians and other aquatic health professionals on the mechanism for reporting adverse drug events.

A second phase of the Animal Health Literacy Campaign we are planning will be a more strategic outreach program to communicate with our key stakeholders – practitioner groups, academia, advocacy groups, trade associations, and others. Through our strategic communication efforts, CVM can communicate more effectively about policy and regulatory responsibilities. Through our communication and outreach efforts we will be better able to shape the context of conversations with stakeholders and build relationships that enhance CVM objectives.

The goal of CVM’s strategic communication campaign is to communicate priority public and animal health messages to key stakeholders. The Center wants to communicate information about emerging issues that are of concern, early in the process, to afford stakeholders an opportunity to work collaboratively to develop strategies to address these public and animal health issues. These stakeholders are most affected by the Center’s policies and regulatory activities and can play a role in addressing issues of mutual interest.

Animal Drug User Fee Program

ADUFA II

In August 2008, the President signed legislation reauthorizing the new animal drug user fee program (Animal Drug User Fee Amendments of 2008, or ADUFA II). The reauthorization of the program came as a result of the success of ADUFA I. It followed negotiations during which FDA worked with the animal health industry to develop performance and budget proposals that would be acceptable to Congress, the industry, and FDA.

The reauthorized ADUFA program will require CVM to continue to complete 90 percent of reviews of non-administrative New Animal Drug Applications and supplemental New Animal Drug Applications within 180 days of their receipt. The 180-day timeframe compares with the goal of 295 days during the first year of the ADUFA program.

Over the 5-year life of the legislation, ADUFA II will provide user fee funding in the amount of $98 million. The user fees will supplement appropriated funding for new animal drug review.

ADUFA II has additional features that will improve the efficiency of the approval process and enhance communication between CVM and the industry. Details are in the section “Increasing the Availability of Safe and Effective Drugs.”

GENERIC DRUG USER FEES

Title 2 of the legislation reauthorizing new animal drug user fees also authorized a user fee program for generic drugs. The Animal Generic Drug User Fee Act of 2008 (AGDUFA) is FDA’s first-ever user fee program to cover generic drugs. Before AGDUFA, the generic animal drug review process had been entirely funded through appropriations.

Under AGDUFA, FDA has promised to meet specific performance goals for generic animal drug review as it begins to collect generic animal drug user fees. For example, FDA has agreed to review 90 percent of non-administrative Abbreviated New Animal Drug Applications within 270 days by FY 2013.

The AGDUFA program calls for user fees to generate a total of $27 million for generic animal drug review over the 5-year life of the measure. More details about AGDUFA are in the section “Increasing the Availability of Safe and Effective Drugs.”

Guidance for Genetically Engineered Animals

The development of genetically engineered animals has progressed to the point that sponsoring firms are nearly ready to introduce commercially a wide variety of products. In September 2008, FDA released draft guidelines to clarify the Agency’s approach to the regulation of genetically engineered animals and to provide industry and other stakeholders an overview of how producers of these animals can meet their responsibilities and obligations in developing them. The guidance will help consumers understand how FDA is overseeing the commercialization of genetically engineered animals and what protections are in place.

Genetically engineered animals were first produced experimentally in the 1980s, and since then the technology has expanded. Some animals were developed to produce pharmaceuticals for humans2, or to provide cells, tissues, or organs for human transplantation. Some will be better able to resist animal diseases, such as mastitis. Still other animals are being developed to produce high-value products for industrial or consumer uses, have less of an effect on the environment, or produce food products with desirable attributes, such as pork with higher levels of omega-3 fatty acids.

CVM will regulate all genetically engineered animals regardless of their intended use, while other FDA Centers and the U.S. Department of Agriculture will have authority over substances produced by GE animals that are within their jurisdiction. The recombinant DNA (rDNA) construct that is engineered to introduce a new trait into an animal fits the definition of a new animal drug; therefore, FDA has regulatory authority.

CVM will review applications for approval of the rDNA construct by using the regulatory structure already in place for the review of new animal drug applications, applying criteria that are unique to genetically engineered animals. CVM scientists will be considering the safety to the animal, effectiveness of the rDNA construct, the safety of any food derived from the animal (if it is intended to enter the food supply), and any possible environmental concern. If the food produced from a genetically engineered animal is different from its non-engineered counterpart, for example if it has a different nutritional profile, in general, that change would be material information that would have to be indicated in the labeling.

CVM has the staff to provide expert, science-based oversight for this technology, including veterinarians, molecular biologists, animal scientists, toxicologists, and risk assessors who have built on CVM’s long-standing experience in assessing animal health and food safety to construct a regulatory framework for genetically engineered animals. Through this work of these experts, CVM has developed what we believe is a rigorous, risk-based approach that ensures the health of genetically engineered animals and the safety of the food that may come from them.

The Critical Path to Improved Public Health

In collaboration with other FDA Centers, CVM received funding for and initiated four Critical Path studies during FY 2008. FDA launched its Critical Path Initiative in March 2004 with the release of a report3 that outlined the scientific reasons for a decrease in the number of innovative medical products submitted for approval. The report called for a concerted effort to modernize the scientific tools (e.g., in vitro tests, computer models, qualified biomarkers, and innovative study designs) and harness the potential of bioinformation used to evaluate and predict safety, effectiveness, and manufacturability of candidate medical products. The focus was on the “critical path” from laboratory concept to commercial product.

The Critical Path Initiative is a comprehensive undertaking to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured. CVM is an active participant in the Agency’s Critical Path Initiative. Here is an overview of Critical Path Initiatives studies initiated in 2008.4

  • A study in collaboration with the FDA Center for Drug Evaluation and Research and the University of Maryland for the development of immediate release oral dosage forms using the concepts of quality by design, predicting in vivo/in vitro correlations (IVIVCs) in dogs and humans, and generating interspecies IVIVC comparisons for low soluble, highly permeable drugs.
  • A study jointly with the Center for Devices and Radiological Health to develop an in vitro method to identify substances that could be toxic to dogs possessing the MDR-1 gene, and to develop an alternative animal model for conducting toxicity tests. This research may eliminate the need to conduct some safety studies in dogs.
  • A study to characterize and evaluate bronchial antimicrobial peptides using an animal pneumonia model, in cooperation with the Center for Food Safety and Applied Nutrition. We anticipate a growing interest in the use of these peptides in animals. The understanding of the properties, function, and efficacy of these peptides will help advance product development and evaluation.

One study addresses the need for timely and accurate monitoring of food and animal feed products for microbiological contamination, particularly resistant organisms.

  • A study to investigate Salmonella diversity that is intended to increase knowledge of how Salmonella disseminate through the food chain and to contribute to the development of rapid response tools for pathogen detection and characterization. We are collaborating with the Center for Food Safety and Applied Nutrition on this project.

CVM scientists who are participating in these studies presented their work during a Critical Path Initiative Workshop, sponsored by the Center for Food Safety and Applied Nutrition and the Drug Information Association in September 2008.

BSE Feed Rule Enforcement: A Decade of Success

OFF TO A FAST START

A decade ago FDA launched what would become an unprecedented inspectional program. We set out to enforce the BSE feed rule, adopted in 1997, to prevent the establishment and amplification of bovine spongiform encephalopathy (BSE) by prohibiting the feeding of mammalian protein (“prohibited materials”) to ruminant animals. The regulation had national and international attention, because of then-recent evidence from the UK that humans could contract a fatal disease (variant Creutzfeldt-Jakob Disease) related to BSE by consuming meat products derived from BSE-infected cattle.

Enforcing the regulation presented a unique challenge. BSE had not been reported in the United States, and there were no practical tests to detect the presence of the causative agent during the preclinical state in live animals. Nor were there practical tests to determine the species origin of protein products found in animal feed. In addition, the regulation reached the activities of thousands of firms in a number of diverse industries – including renderers, protein blenders, and feed manufacturers. Many of these firms had no experience complying with regulations like the BSE feed rule and were not in FDA’s inventory of regulated firms.

Nevertheless, CVM set a goal of 100 percent compliance with the regulation. We wanted compliance not only with the regulation’s paperwork requirements, but also actual compliance – that is, prohibited materials would in fact not be fed to ruminants. We would achieve the goal through a campaign to educate regulated groups and by inspecting 100 percent of the regulated firms in major segments of the affected industries.

During FY 1998, the first year of enforcement, we inspected slightly more than 2,600 firms, approximately 50 percent of all renderers, but only 15 percent of all feed manufacturers. And we found that 15-50 percent of the inspected firms were not in compliance with all aspects of the regulation.

ACCOMPLISHMENTS AT THE MIDWAY POINT

By the end of FY 2003, we had achieved our goal of inspecting 100 percent of the nation’s renderers, protein blenders, and feed manufacturers – more than 6,600 firms – for compliance with the regulation. We had also inspected an additional 6,900 firms including ruminant feeders, on-farm mixers, pet food manufacturers, animal feed salvagers, and animal feed transporters.

In addition, we had nearly reached our goal of 100 percent compliance with the regulation’s requirements; less than 1 percent of the firms known to handle prohibited material had violations serious enough to require official action at their latest inspection. But that was still too many violations – we issued seven Warning Letters and instituted 14 product recalls for violations of the regulation during the year.

5 YEARS LATER – NO SIGNIFICANT VIOLATIONS

FDA and State investigators conducted more than 7,500 inspections during FY 2008. We found no serious violations; thus, no enforcement action was required. From the start of the program in FY 1998 until the end of the fiscal year 2008, we had conducted more than 66,000 inspections at more than 24,000 different facilities.

A decade ago we set a goal of 100 percent actual compliance with the rule. Although there is no way to determine definitively that the goal has been met, inspection results from recent years and the absence of any feed-related BSE cases in the United States suggests that we have effectively achieved full compliance with the feed ban.

A TEAM EFFORT

These achievements were possible only through the efforts of a number of groups and individuals, including FDA District Offices and State agencies, whose investigators have conducted the thousands of inspections; industry associations, who have educated their member firms; and CVM and Agency Headquarters staff, including CVM’s Office of Research scientists, who have done groundbreaking work in developing rapid and efficient test methods for prohibited protein materials.

THE YEARS AHEAD

This year, we turn a page in the history of enforcing the BSE rule. A 2008 amendment of the rule, to expand the scope of prohibited material, presents new enforcement challenges. We describe the rule change, and our efforts to ensure compliance, in the section “Controlling Risk from Bovine Spongiform Encephalopathy (BSE).”

A MESSAGE FROM THE DIRECTOR

CVM Director, Dr. Bernadette Dunham

A Tribute to Dr. Stephen Sundlof

Dr. Steve Sundlof, my predecessor who left CVM to become Director of the Center for Food Safety and Applied Nutrition, is my mentor and friend. It was his vision that led to the publication of the CVM Annual Report, and I am proud to continue the series. Dr. Sundlof was Center Director for more than 13 years; during those years, he most capably led the Center through a number of highly visible and sometimes controversial issues. He initiated a number of undertakings, both within and outside the Center, that have contributed much to the Center’s productivity and contributions to public and animal health. His legacy with CVM is a great one, and we thank him for all that he did.

Celebrating out Accomplishments

This has been an extraordinary year for recognition from outside the Center of the work of our CVM staff members. The details of the recognition are in the opening vignette at the front of this report, in the various sections that describe our accomplishments in various areas, and in the Awards Appendix. I congratulate those on our staff whose efforts bring great credit to themselves, the Center, and the Agency.

But I want also to acknowledge the work of the many staff members whose names do not appear on awards lists or who do not have prestigious assignments to national and international groups. Their efforts – working hard day in and day out to accomplish their assigned tasks, supporting the work of others in many cases – are vitally necessary to the success of the Center’s programs. We thank them for what they – the unsung heroes – do to help the Center accomplish its mission of protecting public and animal health.

We have an enormously talented staff in CVM, with accomplishments that extend well beyond their contributions to their work assignments. We see an example in the excellent set of photographs, taken by staff members, that are displayed throughout this report. It is regrettable that we were unable to publish all of the excellent photographs in this year’s report. However, you can look for them in CVM’s future Annual Reports. I thank everyone who took the time to submit their photographic work.

HIGHLIGHTS OF FY 2008: ACCOMPLISHMENTS THROUGH THE WORK OF OUR PEOPLE

The pages of this report contain descriptions of a great number of accomplishments made by our people during the year, often with the collaboration of our partners and stakeholders. I have selected the following as examples of public and animal health significance, public interest, and level of achievement during the year. You will find more details on each accomplishment elsewhere in this report.

Animal Health Literacy Campaign

We want people to be knowledgeable about current animal health issues, to learn how to apply that knowledge for the benefit of their animals and their own health, and to know that CVM is an important source of relevant information. So when the idea for an Animal Health Literacy Campaign came from staff members within CVM – a result of our efforts to be a high performance organization – Center management enthusiastically endorsed the project. The program got off to a good start in FY 2008, and we intend to expand the program to include strategic interaction with industry groups in the future. As with the “One Health” initiative, veterinarians are key players in increasing animal health literacy levels, and we encourage their involvement in the literacy campaign.

Animal Feed Safety

The melamine-contaminated pet food recall of 2007, and several contamination incidents involving human food, changed the way consumers, Congress, and regulators think about food safety. The incidents highlighted the fact that the United States is part of a global economy, and that imports are a significant part of the human food and animal feed chain. FDA responded with its Food Protection Plan (food = feed) and an Import Safety Action Plan. These plans encompass animal feed, including pet food, which are within CVM’s responsibility. Among other actions, the Agency began the process during the year to establish offices in five foreign locations, starting with China. CVM will be part of this international presence.

The Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the Agency to establish a range of standards, databases and notification systems to protect pets and other animals from unsafe food. We went right to work on this ambitious agenda in FY 2008, holding public meetings, reviewing public comment, drafting documents, and taking other actions leading toward implementation of the Congressional mandates. Our work including taking a close look at a “Pet Event Tracking Network,” a concept proposed during the 50-State Gateway to Food Protection Meeting convened to facilitate implementation of the Food Protection Plan. The Pet Event Tracking Network would be an early warning system to detect companion animal feedborne outbreaks and would provide Federal regulators the opportunity to partner with State and local health organizations.

Our research staff developed a method for detecting melamine in pet food in FY 2007. Then, in FY 2008, with the news of melamine contamination of infant formula in China, our scientists quickly modified the method so that it could be used in detecting melamine in infant formula – this time protecting human health!

Extension and Expansion of User Fees to Expedite New Animal Drug Approvals

Building on the success of the Animal Drug User Fee Act of 2003 (ADUFA I) – kudos to our Office of New Animal Drug Evaluation, which has met every ADUFA goal so far – and acknowledging the need to speed the approval process for generic new animal drugs, Congress passed two laws this past year: the Animal Drug User Fee Amendments of 2008 (ADUFA II), and the Animal Generic Drug User Fee Act of 2008. CVM participated actively with industry associations in the negotiations leading to the passage of these new laws. When ADUFA II went into effect October 1, 2008, the Office of New Animal Drug Evaluation was ready with updated procedures and training for implementation of the law’s new features that will make the program even better for the industry and CVM. With the new laws, we plan to do more to improve the efficiency and effectiveness of our drug review program, both for pioneer and generic applications.

Guidance on Controversial Pre-Market Decisions

When we set about preparing and releasing guidance on two controversial subjects – genetically engineered animals and animal clones – we knew that we needed to utilize the best science, develop a clear regulatory policy, and communicate the relevant information to the public in an understandable manner. Working with experts elsewhere in the Agency, our staff did a superb job.

Our draft guidance document on genetically engineered animals provides timely information on the regulatory environment – including specific guidance on pre-market approval requirements – to genetically engineered animal sponsors who are approaching the commercialization stage. Importantly, the guidance also describes to the consumer the protections in place to ensure the safe use of this technology.

The number of comments we received on the draft animal cloning risk assessment – 30,000 – highlighted the level of public concern and controversy on this topic. We knew that release of the final draft – which confirmed our position that clones and their progeny from several animal species are as safe as food from conventional animals and therefore do not need pre-market approval – would need to be done with great care. So we made it clear to the public as we released the risk assessment that we based all our decisions about food and animal safety on the best science available, using extensive amounts of data, and that we were working openly and using only publicly available information. We worked with communications experts on FDA’s staff to make sure we delivered complete, accurate, and understandable information to consumers.

During the year we continued to be at the forefront of the rapidly developing One Health Initiative. One Health is the collaborative effort of multiple disciplines – working locally, nationally, and globally – to obtain optimal health for people, animals, and our environment. Nearly two dozen Federal and State agencies and professional and scientific organizations – including the American Medical Association and the American Veterinary Medical Association – are participants.

The increasing threats posed by emerging zoonotic diseases (those that can be transmitted from animal to humans), food and waterborne diseases, and environmental change led to the creation of the initiative.

Because the scope of One Health includes animal health, CVM is squarely within the parameters of the initiative. Here are three examples:

  • Avian influenza.Our scientists made progress during the year in developing methodology to detect use of certain antiviral drugs in poultry. The methodology will be used to enforce CVM’s order prohibiting the use of those drugs in poultry. The goal is to preserve the drugs’ efficacy for human use in the event of an influenza pandemic.
  • Foodborne antimicrobial resistance.This past year brought renewed attention to the effort, long led by CVM, to reduce resistance-related risk to human health from the use of antimicrobials in animals. For example, Congress included in ADUFA II a reporting provision related to the marketing of antimicrobial drugs, and Congress held hearings on the subject of antimicrobial resistance during the year. Our scientists continued to provide leadership and scientific expertise on this issue, on a national and international basis. They worked not only to help other nations cope with resistance issues, but also to ensure that decisions of other nations and international bodies will be based on objective evidence for determining the degree of risk.
  • Bovine spongiform encephalopathy (BSE). Scientific evidence strongly suggests that humans can contract variant Cruetzfeldt-Jakob Disease by consuming meat products derived from BSE-infected cattle. Compliance during the past decade with our BSE feed rule, which is aimed at protecting both animal and human health, is one of the most impressive regulatory accomplishments in which CVM has participated. The success is a result of a joint effort involving FDA, State regulatory agencies, livestock production industries, the feed and rendering industries, and others. This year, we began gearing up for a new level of public protection – we have been training inspectors, coordinating with industry on education programs, and otherwise preparing to implement the amended BSE feed rule that expands the prohibition on use of cattle protein in animal food.

One Health Initiative

Promoting Public Health at the Animal/Human Health Interface

“Through mutual collaborations – clinical and research experiences – veterinarians and physicians can accomplish so much more together to advance the health of humans and animals. Today, we truly live in a global village where people, animals, and microbes all travel. So, it is even more imperative that we all embrace the One Health initiative. I look forward to joining my colleagues in a multidisciplinary approach as we address the global health needs of humans, animals, and their environment.” Dr. Bernadette Dunham

Meeting Department and Agency Goals

As highlighted throughout this report, our performance goals are aligned with Department of Health and Human Services and FDA objectives and goals. As in the past, we have indicated whether we reached our performance objectives and goals for the fiscal year that this report covers. For FY 2008, we were able to achieve all of our performance objectives and goals. Congratulations to our dedicated staff.

A Message to Partners and Stakeholder Groups

From the time of my appointment as Center Director in January 2008, I have placed high priority on outreach – meeting with those who have a stake in what we do. I have had the opportunity to meet a wide range of people, including representatives of industry and producer groups, and individual firms; organizations representing veterinarians; consumer and animal interest groups; and scientific and technical organizations. I have had extensive interaction, both here and in other countries, with representatives of international regulatory agencies and foreign embassies. These meetings have involved a wide range of topics, from drug approval and other regulatory policies, to aquaculture and minor species policies, to harmonization and collaboration on an international basis, and to a number of other subjects including partnership activities and arrangements.

This has been a valuable “get acquainted” and learning time, a time of laying a solid foundation for collaboration in areas of mutual interest, and for helping stakeholder groups build their programs in a way that is compatible with CVM’s regulatory responsibilities. I have been excited to participate in coalition building efforts as we formulate plans for future implementation.

CVM has always stressed good communications with stakeholders. Good communication benefits stakeholders and consumers as it fosters progress in public health protection. We have an open door policy, and we embrace being transparent in our plans and actions. Please feel free to share your comments and to come and meet with us.

Partnerships with people and organizations outside the Center are a key part of CVM’s success story. This Annual Report documents continued expansion of collaborative activities with many of our stakeholders and partners. These arrangements provide mutual benefit and allow us to fulfill our role in protecting the public health more effectively and efficiently.

A Message From The Center Leadership Team5

We have the privilege of following Dr. Dunham’s highlights of the Center’s substantive FY 2008 achievements.

We are continually reminded as we do our day to day work how fortunate we are to be a part of such a great organization. What makes CVM special is our cadre of hard working, motivated, and talented people. Each member of CVM makes a difference, and together in FY 2008 we accomplished much. We, the Center Leadership Team, are proud to work with our CVM colleagues and are very optimistic about meeting the challenges of FY 2009 and beyond.

The charge given us, as members of the Center Leadership Team, is to help ensure that CVM is a center of excellence at FDA while staying true to our vision and values. We meet regularly to collaborate on day-to-day management and policy decisions facing the Center, as well as long-range strategic planning, budgeting, and policy development.

Our values include fairness, diversity, excellence, integrity, effective communication, respect for each other and our organization, and a strong work ethic. And as leaders we must constantly challenge ourselves and ask questions such as: What are we doing as a leadership team and as a Center to uphold our values? How do we achieve and maintain a participative/collaborative work culture?

Intrinsic in CVM’s leadership philosophy and values is the concept of “stewardship.” Merriam-Webster’s dictionary defines stewardship as “the conducting, supervising, or managing of something; especially: the careful and responsible management of something entrusted to one’s care, e.g., stewardship of our natural resources.” Stewardship can also be applied to organizations, especially those like FDA and CVM that serve the public and are dedicated to public and animal health protection. We believe that each individual shares the responsibility for the stewardship of the Center and the success of the entire organization.

In our decision making and policy development we encourage each individual to consider not only the impact on one’s work unit but also on the success of the Center as a whole. Our philosophy is that leadership belongs to everyone.

Consistent with our value of fairness, we are also very proud of the fact that CVM is out in front of FDA’s scientific dispute resolution initiative. Our internal dispute resolution policy, “Procedures for Internal CVM Review of Science or Policy Issues Related to Significant Decisions of High Impact,” which addresses how to handle differences of thought or opinion within CVM, has served as a model for FDA. We as leaders recognize that diverse opinions yield better decisions. The Center welcomes people putting forward their points of view in an environment that is free of retribution. The process for making decisions on science and policy allows and even depends on differing perspectives and concerns. When differences do arise, we strive to resolve them in a way that builds relationships and opens future lines of communication.

As an organization, we realize we also have to be successful in hiring talented new staff members and retaining and helping our existing staff succeed. We feel that enabling employees to grow is the best retention strategy; and the best way to implement that strategy is for us to live our core belief that “leadership belongs to everyone,” a reflection of CVM’s philosophy of stewardship and the Center’s participative culture.

We have created leadership development programs for all who aspire to enhance their leadership skills. In support of the CVM succession plan and to ensure the development of a cadre of talented and ready employees for CVM, we focus on strengthening the talent and skills of everyone in the organization, regardless of the person’s job, role, or position. We develop our employees as they enter the organization rather than starting their development near the peak of their career.

Our leadership development programs, in addition to course offerings, consist of mentoring, coaching, and other development activities, all of which serve as powerful catalysts for our continuous learning, advancement, and growth. In the past year alone we developed three Center-wide competency-based leadership development programs.

This year has been challenging, busy, and productive. We are looking forward to working with the new Administration, our new Secretary of Health and Human Services, and a new FDA Commissioner as we continue our work to promote and protect the public and animal health. We hope that you enjoy this Annual Report and through it you realize as we do that CVM is a very special organization.

About CVM

Our Mission and Guiding Principles

OUR MISSION…

The Center for Veterinary Medicine is a consumer protection organization. We foster public and animal health by approving safe and effective products for animals and by enforcing other applicable provisions of the Federal Food, Drug, and Cosmetic Act and other authorities.

OUR GUIDING PRINCIPLES…

We are committed to:
Health Protection. We honor our role in protecting the health of people and animals, and value the principles and spirit of the supporting laws and regulations.

Integrity. We conduct ourselves with honesty and integrity, recognizing that upholding the public trust requires the highest standards of moral and ethical conduct.

Quality. We achieve excellence through the ongoing development of our competencies and continuous quality improvement in all our processes. In particular, we recognize the value and importance of science and law in reaching quality and timely regulatory decisions.

Teamwork. Everyone’s contribution is important. Working together, we place the mission of the Center first and align our contributions, whether individual or in teams, toward that end. We conduct ourselves in accordance with the principles of consultative and participative decision-making.

Communication. We communicate information, ideas, decisions, and provide feedback, internally and externally to the organization, in a candid, timely, constructive, and clear manner.

Equity. We treat our customers and each other with fairness, courtesy, respect, and compassion, while fostering an atmosphere of mutual trust.

Diversity. We promote workforce diversity to strengthen and enrich the Center.

Innovation. We apply new concepts, ideas, and creative approaches to improve current operations and to meet the challenges of the future.

Safety and Health. We seek to ensure a safe and healthful workplace.

Quality of Worklife. We create and use programs that enhance our quality of worklife to improve our ability to carry out the mission of the organization.

Our Strategic Plan

CVM’s strategic plan reflects the principles set forth in the President’s Management Agenda, the 500-Day Plan initiative of the Secretary of Health and Human Services, and the Food and Drug Administration’s Strategic Goals.

Our plan, “CVM’s Back to Basics Approach for Carrying Out Our Public and Animal Health Mission,” commits us to focus on our core functions of:

  • Animal drug review (pre-market activities);
  • Compliance-related actions;
  • Post-approval monitoring; and
  • Animal feed safety.

To help us focus on the basics, our plan establishes the following goals. We will:

  • Set priorities (reviewed annually) and say “no” to lower priority items;
  • Improve, and bring discipline to and through, our business practices;
  • Support and use good science in establishing solid regulatory policy;
  • Improve the capacity of the organization to meet
    current and future demands on the Center; and
  • Develop revenue enhancing strategies for core programs.
Our Organization and Responsibilities

We carry out our mission through the efforts of people who are organized into six offices: the Office of the Director; the Office of Management; the Office of Minor Use and Minor Species (MUMS) Animal Drug Development; the Office of New Animal Drug Evaluation; the Office of Surveillance and Compliance; and the Office of Research. All of our offices are located in Rockville, MD, except the Office of Research, which is located in Laurel, MD.

OFFICE OF THE DIRECTOR

The Office of the Director directs overall Center activities, and coordinates and establishes Center-wide policy. The Center Director serves as CVM’s primary representative and spokesperson concerning our activities, interacting with the general public, industry, the media, other government agencies, and national and international organizations.

The Office of the Director conducts communication and education programs, coordinates policy development and implementation, provides project management support for the Center, offers the services of the CVM Ombudsman, manages the Veterinary Medicine Advisory Committee, and coordinates the Center’s international activities. The Office of Animal Care and Use, located in the Office of the Director, coordinates accreditation and compliance with regulatory requirements of the Agency’s animal care and use programs, and provides consultation on these issues. The Center’s international work is also coordinated through the Office of the Director.

OFFICE OF MANAGEMENT

The Office of Management provides executive leadership and direction for management and administrative programs, policies, and issues at Center and Agency levels. The Office’s management staff serves in strategic leadership positions on CVM and FDA councils and committees. The Office provides the Center’s liaison services to the Agency’s Office of Shared Services, the Rockville Human Resources Center, and the Office of the Chief Information Officer to ensure efficient administrative services, as well as the effective delivery of information resources management services to CVM employees.

The Office of Management leads and directs the planning, development, and execution of the CVM budget, including the user fee programs, which includes a generic animal drug user-fee program beginning in FY 2009. It also serves as the Center liaison with the Agency concerning Government Accountability Office and Inspector General studies/inquiries. The Office provides leadership for the Center’s Activity-Based Costing/Activity Time Reporting System, integrating it into the business culture of the Center’s operation, and provides guidance for the implementation of the Center’s strategic plan.

The Office of Management directs the interaction with the CVM program offices and other FDA offices to assist with the efficient delivery of such services as travel, property management, space and workplace planning, facilities management/operations, and workplace safety. In addition, the Office represents management on issues regarding the FDA and National Treasury Employees’ Union Collective Bargaining Agreement.

The CVM Staff College, also within the Office of Management, directs the development and implementation of the competency-based professional development programs in management and leadership, as well as an extensive scientific and emerging technology curriculum. The Staff College coordinates and manages the delivery of collaborative programs with academic institutions and serves as learning consultants for Center employees in competency development activities.

The Office of Management supports the vital information resources management function to enhance employees’ abilities to efficiently work with the integrated Information Technology systems to reach CVM goals.

OFFICE OF MINOR USE AND MINOR SPECIES ANIMAL DRUG DEVELOPMENT

The Minor Use and Minor Species Animal Health Act of 2004 (MUMS Act) provided for the establishment of the Office of Minor Use and Minor Species Animal Drug Development. The Office reports directly to the CVM Director and is responsible for overseeing the development and legal marketing of new animal drugs for minor uses in major species (disease conditions that are rare in cattle, horses, swine, chickens, turkeys, dogs, and cats) and minor species (including, for example, pet animals such as ornamental fish, parrots, ferrets, guinea pigs, and iguanas, zoo animals; and species of agricultural importance such as sheep, goats, commercially produced fish such as catfish and tilapia, and honeybees).

The Office of Minor Use and Minor Species Animal Drug Development participates in the drafting of, and administers the MUMS Act implementing regulations such as those relating to Designation, Indexing, and Conditional Approval. This responsibility may involve a determination of whether the intended use of a new animal drug qualifies as a minor use in a major species. The Office also performs a liaison role to the U.S. Department of Agriculture’s minor use research program (National Research Support Project #7), and provides outreach to stakeholders – including veterinarians, producers, consumers, government agencies, and the regulated industry.

OFFICE OF NEW ANIMAL DRUG EVALUATION

The Office of New Animal Drug Evaluation administers the core function of drug review, which involves directing the approval process for animal drugs. FDA must review an animal drug for safety, effectiveness, and quality before the drug can be legally marketed in interstate commerce. CVM evaluates drugs intended to benefit the health and productivity of food animals and the health of companion animals. CVM has drug regulatory authority over articles (other than food) that affect the structure or any function of an animal’s body.

Drug sponsors must submit tests to establish drug safety and effectiveness. Sponsors of drugs intended for food animals must also prove that food products derived from treated animals do not contain unsafe drug residues and that the food products are safe with respect to microbial safety. The sponsors must develop analytical methods to detect and measure drug residues in edible animal products. The Federal Food, Drug, and Cosmetic Act provides for approval of both pioneer and generic animal drugs and for FDA-granted authority to use investigational animal drugs. CVM classifies the animal drugs it approves, for distribution and use purposes, as over-the-counter, prescription, or veterinary feed directive.

The Office of New Animal Drug Evaluation administers the performance aspects of the Animal Drug User Fee Amendments of 2008 and the Animal Generic Drug User Fee Act programs, which authorize FDA to collect user fees in support of the review of new and generic animal drugs. Under the Acts, CVM agreed to pursue a comprehensive set of review performance goals to improve the timeliness and predictability of the review of new and generic animal drug applications and investigational animal drug submissions.

OFFICE OF SURVEILLANCE AND COMPLIANCE

The Office has primary responsibility for three of CVM’s four core functions: compliance-related actions, post-approval monitoring, and animal feed safety. The Office of Surveillance and Compliance monitors the safety and effectiveness of approved drugs after they enter the market. Working with the U.S. Department of Agriculture and State agencies, the Office monitors the occurrence of unsafe drug residues in meat, milk, and poultry products, and guides efforts to protect consumers through educational and enforcement activities related to drug residues. The Office coordinates enforcement actions against unapproved drugs that are on the market and that threaten public and animal health. The Office regulates the promotion and advertising of animal drugs to ensure that they are promoted in a truthful and non-misleading way and each year receives more than 35,000 adverse drug events that are used to provide updated safety and effectiveness information to consumers.

Working with epidemiologists in CVM’s Office of Research, the staff of the Office of Surveillance and Compliance utilizes epidemiological skills to protect public and animal health.

The Office of Surveillance and Compliance conducts programs to protect animal feed from contamination by toxic materials such as mycotoxins, pesticides, heavy metals, and industrial chemicals, and to prevent the establishment and amplification of bovine spongiform encephalopathy (BSE) through feed. The Office administers the feed mill licensing program and coordinates biennial inspections of medicated feed manufacturers. It approves food additives for use in animal feed and reviews genetically modified plant varieties for safety. The Office coordinates the Center’s counterterrorism efforts. The Office’s Bioresearch Monitoring Team oversees inspections of both nonclinical (laboratory) and clinical studies to provide assurance of the integrity of data submitted in support of animal drug applications. The Office also coordinates the Center’s administrative actions involving approved drugs, such as actions to withdraw drug approvals.

OFFICE OF RESEARCH

The Office of Research is the laboratory-based research arm of CVM and conducts applied research in support of regulatory decision-making related to each of CVM’s core functions. The Office of Research is housed in a state-of-the-art research complex located on 166 acres of land, including approximately 38 acres of pasture, in Laurel, MD. The complex consists of offices, laboratories, animal research buildings, and support facilities. The Office of Research is staffed by researchers with diverse scientific backgrounds – microbiology, biochemistry, toxicology, analytical chemistry, pharmacology, veterinary medicine, etc. – as well as scientists with specialized training e.g., aquatic science specialists and molecular biologists.

The Office of Research’s research priorities are ever changing, being driven by the needs of other CVM offices – i.e., the Office of New Animal Drug Evaluation, the Office of Minor Use and Minor Species, Animal Drug Development and the Office of Surveillance and Compliance, and by FDA-wide requirements to thoroughly address the latest food and drug safety concerns (e.g., BSE, melamine, antimicrobial resistance).

In support of the drug review function, the Office of Research conducts studies in animal drug safety and effectiveness, antimicrobial resistance mechanisms, metabolism, standardization of test methods, and pharmacokinetics/pharmacodynamics. The Office supports the compliance program of the Center through the development of analytical methods and evaluation of screening tests for detection of drug residues in imported and domestic food products. The position of Director of the National Antimicrobial Resistance Monitoring System (NARMS) resides within the Office of Research, and the Office is responsible for the monitoring of retail meats for antimicrobial resistant foodborne bacterial pathogens under NARMS.

These pathogens are also subjected to molecular typing as part of the national PulseNet program. The Office of Research has an animal feed safety research program focusing on developing and evaluating microbiological and analytical methods for detection of natural and intentional contaminants, e.g., melamine, antimicrobial resistant bacteria, and the safety of new feed components, such as dried distiller’s grains. The Office is also developing methods to detect material prohibited by the BSE feed regulation that could compromise animal feed safety.

The Office of Research prepares a detailed annual report. For a copy, write to: Center for Veterinary Medicine, Office of Research, 8401 Muirkirk Road, Laurel, MD, 20708, attention Ms. Gina Weems or Ms. Karen Taylor.

Our Sphere of Influence

CVM’s efforts to help ensure that domestic and imported animal food products are safe affect millions of consumers. On the average, American consumers eat 110 lbs. of meat, 74 lbs. of poultry, 16 lbs. of fish, 600 lbs. of dairy products, and 30 lbs. of eggs each year. Besides protecting the health of consumers in a population that has now passed 300 million, CVM works to safeguard the health of food-producing animals in the United States: 8.9 billion chickens, 262 million turkeys, 97 million cattle, 62 million pigs, and 6.2 million sheep are produced each year. The United States now produces more than $100 billion worth of livestock and livestock products each year.

CVM approvals are now in effect for several hundred animal drug applications, including generics, for use in food-producing animals. We have approved many of these drugs for administration through animal feed. Under a law passed by Congress in 1996, CVM began licensing firms that manufacture certain medicated feeds; presently, there are 990 licensed feed mills. In addition, we have published regulations that authorize use of more than 50 food (feed) additives. Several hundred approved drug applications, including generics, are available to maintain the health of our nation’s growing population of pets, which now includes 65 million dogs and 75 million cats, in addition to 11 million birds and 6 million horses.

FDA is responsible for ensuring the safety of all animal feed and feed ingredients mixed by commercial and noncommercial feed manufacturers. We estimate the number of firms, including livestock and poultry producers and firms in a variety of specialized industry groups, to be at least 90,000. We also regulate nearly 400 animal drug manufacturers and other sponsors of animal drug applications and Type A medicated articles (new animal drugs intended for use in the manufacture of medicated animal feed).

The drugs we approve help the Nation’s more than 70,000 veterinarians accomplish their task of maintaining the health of the Nation’s animals.

Our Stakeholders and Partners

OUR STAKEHOLDERS

Many organizations and millions of individuals have a stake in the outcome of CVM’s work, including consumers, animal owners, veterinarians, and firms in the regulated industries – companies that market the drugs, feeds, and other products that we regulate. Our stakeholders also include trade associations; consumer organizations; State, Federal, and foreign regulatory agencies; and international standard-setting organizations.

We use a variety of methods to keep stakeholders informed, and to seek their advice and opinions about our policies and programs. These methods include public meetings; requests for comment on proposed regulations and guidance documents; the CVM Web site; and a variety of informal means, such as letters, phone calls, and e-mails.

OUR PARTNERS

Our success in promoting and protecting the public health depends not only on the active involvement of our stakeholders, but also on the formation of partnerships and coalitions. The concept of collaboration and partnership is generally known as leveraging, and we are working to make it one of the foundations of our day-to-day operations. A partial list of our partners includes:

  • Other Federal agencies with whom we share related regulatory responsibilities, such as the U.S. Department of Agriculture’s Food Safety and Inspection Service (e.g., surveillance for animal drug residue and antimicrobial resistance), Animal and Plant Health Inspection Service (e.g., BSE), and the U.S. Environmental Protection Agency (e.g., pesticides). For example, the Interagency Residue Control Group, with members from FDA, the U.S. Department of Agriculture, and the Environmental Protection Agency, coordinates information on residues of animal drugs, pesticides, and environmental contaminants in animal food products.
  • U.S. Fish and Wildlife Service and State natural resources agencies (e.g., sharing of data for approval of drugs for minor species).
  • Centers for Disease Control and Prevention, National Center for Infectious Diseases (e.g., surveillance for antimicrobial resistance).
  • The U.S. Department of Agriculture’s Foreign Agricultural Service, Agricultural Research Service, and Cooperative State Research, Education, and Extension Service.
  • State agencies, which partner with us to conduct inspections for compliance with the BSE feed regulation and other feed inspections and to carry out other regulatory and surveillance functions. We work very closely with the Association of American Feed Control Officials. The Association’s membership consists of representatives from all 50 states, Puerto Rico, Costa Rica, Canada, FDA, U.S. Department of Agriculture, and several universities.
  • Veterinarians, who share with us numerous public and animal health goals, such as approval of new and better therapeutics, avoiding drug residues in food products, minimizing the development of antimicrobial resistance through prudent drug use practices, educating food animal producers as to their public health responsibilities, and educating pet owners as to proper drug use.
  • Foreign regulatory agencies that have responsibility and authority for controlling animal drugs and feeds in their countries. We leverage such international work through our participation and leadership in the Committee on Residues of Veterinary Drugs in Foods of the Codex Alimentarius Commission; The World Organization for Animal Health; the European Food Safety Authority; the International Cooperation on Harmonisation of Technical Requirements for the Registration of Veterinary Medicinal Products; and other multilateral organizations.

We partner through cooperative agreements, cost-sharing contracts, cooperative research and development agreements, interagency agreements, cosponsorship agreements, and informal agreements. We hold joint workshops, cosponsor training sessions, work with scientists on mission-related research, and cooperate with others in many ways. We include a number of examples of current partnership arrangements in this Annual Report.

Fiscal Year 2008 Challenges And Accomplishments

INTRODUCTION

Although we are organized into six separate offices, our Guiding Principles call for the staff of the Center for Veterinary Medicine to work together, placing the mission of the Center first. In fact, most of our significant accomplishments involve the efforts of people from two or more offices, through teams, committees, and day-to-day coordination.

Thus, we organize our presentation of FY 2008 accomplishments not according to office structure, but according to crosscutting topics. These topics reflect issues of significant public interest, and illustrate the interoffice and interdisciplinary nature of CVM’s work. We introduce each of these areas of concern with a statement of the challenges that we face as we attempt to meet our “Back to Basics” goals, and Agency and Department objectives.

Accomplishing Department and Agency Objectives

The Department of Health and Human Services established a number of broad-ranging objectives for FY 2008, and FDA adopted these objectives to guide the Agency in carrying out its mission to protect the public health. The objectives are divided into program results, and executive leadership and management results. Following are examples from our report card to show our success in achieving these objectives; details are in Appendix F.

PROGRAM RESULTS

Our report card is based on an analysis of our achievements with respect to each of the performance objectives. A √ for an objective means that we accomplished all of the elements within the objective. Selected program results objectives for FY 2008, with brief explanations or examples, follow.

Selected Program Results

Implement requirements of the Food and Drug Administration Amendments Act of 2007 (FDAAA) within prescribed timeframes.

FDAAA requires the Agency to establish standards, databases, and notification systems to protect pets and other animals from unsafe food. Our program objective in FY 2008 was to accomplish key deliverables or milestones in the Commissioner’s FDAAA Implementation Plan, within prescribed timeframes and at a high level of quality.

Strengthen Critical Path/Science.

We were challenged to exercise leadership in a multidisciplinary approach to identify and develop interventions for the reduction of enterohemorrhagic E. coli O157:H7 in cattle. That organism, which can cause illness and death in humans, may be transferred from cattle to humans through ground beef. During the year, we worked with the U.S. Department of Agriculture with a goal of developing standard endpoints for studies to determine the effectiveness for reduction claims for E. coli O157:H7 in cattle. These studies could be used in the development of vaccines and drugs intended for the reduction of enterohemorrhagic E. coli O157:H7 in cattle. We developed other critical path initiatives, as described elsewhere in this report. By these and other critical path initiatives we have advanced the FDA’s scientific knowledge and acumen in animal drug evaluation.

Increase access to new animal drugs by the timely review of New Animal Drug Applications.

We have accomplished goals under the Animal Drug User Fee Act for application review times and other actions to improve the animal drug application review process.

Negotiate a reauthorized Animal Drug User Fee Act (ADUFA) √ and an Animal Generic Drug User Fee (AGDUFA) program.

CVM representatives co-chaired the successful negotiations with industry for the reauthorization of ADUFA and authorization of AGDUFA that included primary responsibility for development and acceptance of the financial package, and delivering the completed package to the Department within prescribed timeframes.

Antimicrobial resistance – Implementation of Guidance for Industry # 152.

We employed our Guidance for Industry (“Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern”), GFI #152, for evaluating critically important and highly important antimicrobials, emphasizing risk mitigation, communication, and refined release assessment. We assisted 18 drug sponsors of 35 different compounds to consider how microbial food safety information can be used to specify conditions of use that will not adversely impact public health. The impact of these initiatives is increased predictability and transparency, allowing the public to better understand microbial safety requirements.

Pandemic influenza preparedness.

A method capable of detecting four antiviral compounds and a known metabolite of one compound was developed. Metabolism studies were started to verify the choice of the marker compounds.

Guide CVM efforts through the FDA Bioinformatics Board decision-making process to ensure CVM business and IT needs are met.

Through Office of Management efforts in FY 2008, CVM has evolved a more mature process for managing its IT investments and identifying its IT requirement to the Bioinformatics Board, thereby enabling FDA Bioinformatics Board to better support CVM’s mission needs.

Establish collaboration between CVM and the Center for Devices and Radiological Health to leverage existing software and applications to meet CVM electronic submission needs through the FDA/CVM Electronic Document Storage and Review Project.

CVM collaborated with FDA’s Center for Devices and Radiological Health to improve business processes for a more robust electronic document management and submission environment.

EXECUTIVE LEADERSHIP AND MANAGEMENT RESULTS

In additional to the program objectives discussed above, we were challenged to achieve a number of Department- and Agency-wide objectives related to executive leadership and management results. We achieved all of the executive leadership and management objectives within CVM’s scope of responsibilities. We provide further details on leadership and management objectives in “Achieving Productivity Through Achievement of Leadership and Management Objectives” and elsewhere in this report.

Increasing the Availability of Safe and Effective Animal Drugs

THE CHALLENGE

Statutory standards and the needs of our stakeholders – and especially the needs of the billions of animals whose health we seek to protect – require that we make the right animal drug pre-approval decisions, and do so efficiently and expeditiously. The Animal Drug User Fee Act of 2003 (ADUFA, amended in 2008) and the Animal Generic Drug User Fee Act of 2008 (AGDUFA) provide sufficient revenue for CVM to sustain an efficient and effective process for the review of pioneer and generic new animal drug applications. The challenge for CVM is to administer these programs so as to increase the availability and diversity of safe and effective drugs to meet the therapeutic and production needs of animals.

FY 2008 ACCOMPLISHMENTS

This year, CVM had two substantial accomplishments relative to the pre-market evaluation of new animal drugs. These achievements came as a result of the successful negotiation and passage of the new AGDUFA, and the 2008 reauthorization of the Animal Drug User Fee Act of 2003.

ANIMAL GENERIC DRUG USER FEE ACT (AGDUFA)

The success of the Animal Drug User Fee Act of 2003 did not carry over to the generic animal drug review process, because the law did not apply to generic animal drugs. The contrast in review efficiency was substantial. In response to the disparity, the generic animal drug industry – represented by the Generic Animal Drug Alliance – made a proposal for legislation that would provide needed resources through a series of user fees to improve the efficiency and timeliness of the review of generic animal drugs by CVM. AGDUFA was signed into law by President Bush on August 14, 2008, and became effective October 1, 2008 (the beginning of FY 2009). It is the first generic user fee law applicable to drugs regulated by the FDA.

The purposes of the new law are to establish a program of fees for the review of generic animal drug submissions and to improve the timeliness and predictability of the process for generic animal drug submissions.

AGDUFA establishes three different kinds of user fees: (1) fees for certain types of abbreviated applications for generic new animal drugs, (2) annual fees for certain generic new animal drug products, and (3) annual fees for certain sponsors of generic animal drug applications and/or investigational submissions for generic new animal drugs. AGDUFA has many similarities to ADUFA. The major differences are that AGDUFA does not provide for the collection of establishment fees, and FDA may waive or reduce fees only if the generic drug is intended for a minor use or minor species indication. In addition, the sponsor fee is graduated based on the number of approved Abbreviated New Animal Drug Applications (generic applications) held by the sponsor.

User fees provided for through AGDUFA will generate a total of $27 million for generic animal drug review over the 5-year life of the measure. The funding provides for more efficient and timely review of generic animal drug submissions, for training and development of staff members, and for refining business processes and adopting policies to allow more efficient review of generic animal drug submissions.

Under AGDUFA, FDA is required to meet specific performance goals for generic animal drug review as it begins to collect user fees. By FY 2013, the fifth year of AGDUFA, the goal will be to review 90 percent of non-administrative original Abbreviated New Animal Drug Applications within 270 days.

AGDUFA ensures a sound financial footing enabling FDA to improve product review performance, reducing the time required for safe and effective generic animal drugs to reach the marketplace, and supporting the Department of Health and Human Services objective for rapidly approving safe and effective new drugs.

ANIMAL DRUG USER FEE AMENDMENTS OF 2008

“There is general agreement that ADUFA has been successful in eliminating the review backlog and has improved the timeliness and predictability of reviews.”6

This statement provided a foundation for the passage of a 5-year extension of ADUFA, which was set to expire on September 30, 2008. President Bush signed the Animal Drug User Fee Amendments of 2008 (ADUFA II) on August 14, 2008. CVM had an active role in the reauthorization of the legislation, including participating in negotiations with representatives of the animal health industry through the Animal Health Institute.

Congress passed ADUFA in 2003 in response to reports from FDA documenting inadequate resources for application review, growing workloads, and increasing review times. The animal drug approval process had slowed to an unacceptable pace. ADUFA required that sponsors of new animal drugs provide sustained revenue for the FDA new animal drug review program through a series of fees. Specifically these included: application fees for each original and supplemental New Animal Drug Application, annual manufacturing establishment fees, annual product fees, and sponsor fees. These added resources are all in an effort to expedite the animal drug review process.7

The original ADUFA set a goal of completing 90 percent of reviews of non-administrative original and supplemental New Animal Drug Applications within 180 days of their receipt in FY 2008 – down in yearly increments from the 295-day target during the first year of the ADUFA program (FY 2004). We met or exceeded the goals for the first four years, FY 2004 to FY 2007. (The data for FY 2008 were not available for this Annual Report.) During FY 2008 we worked to achieve goals set for the final year of the original ADUFA. Performance and financial reports for FY 2008 will be published separately.

FDA was authorized to collect $43 million (plus inflation) in user fees under the original ADUFA; the target for the next 5 years under ADUFA II is $98 million. With respect to performance goals, ADUFA II maintains the FY 2008 timeframes, including 180 days for review of original and supplemental applications (the long-standing statutory goal).

ADUFA II also includes several new provisions to enhance the animal drug evaluation process. These provisions include:

  • The “end review amendment” process, which will enable FDA to work with a drug manufacturer to make corrections to address deficiencies at the end of the review process, rather than causing another cycle of submission and review. This will improve efficiency by significantly reducing the number of submission review cycles.
  • Ten public workshops on topics mutually agreed to by FDA and the regulated industry, to be conducted during the 5-year life of ADUFA II.
  • Improvements to the information technology infrastructure of the animal drug review process. Within two years of receiving funding, CVM will develop an electronic tool for industry submissions that will have online review capability.
  • The timeliness and predictability of foreign pre-approval inspections is to be improved. Sponsors will be able voluntarily to notify FDA in advance of a submission, describing their manufacturing processes and addressing the need for a pre-approval inspection for their animal drug product. This advanced notification will allow FDA to conduct pre-approval inspections in a timely manner.

The ADUFA II performance goals also set the stage for enhanced communications between the regulated industry and FDA to explore new approaches to the demonstration of safety and effectiveness of new animal drugs including the use of pharmacokinetic information.

The reauthorization of ADUFA ensures a sound financial footing that enables FDA to continue achievement of performance goals at the FY 2008 levels, and add new performance goals. ADUFA II continues to support the Department of Health and Human Services objective for rapidly approving safe and effective new drugs, including drugs for food animals that are safe for the consumer.

FY 2008 APPROVALS

We have listed significant FY 2008 new animal drug approvals in Appendix B. We have also highlighted several of these approvals for companion animals, and for minor uses/minor species, in the sections related to those topics. The significant approvals include the addition of more than 17 new therapeutic options to previously approved new animal drug applications. Examples of approvals for food animals include a new indication for the antimicrobial DRAXXIN (tulathromycin) Injectable Solution, for the treatment of infectious bovine keratoconjunctivitis (pinkeye), and BAYTRIL 100 (enrofloxacin) for a new species and indication through approval of the drug for swine respiratory disease.

IMPROVING THE EFFICACY AND EFFECTIVENESS OF THE REVIEW PROCESS

Enhancing the Review Process Through the Development of Regulations and Guidance Documents

Regulations and guidance documents are important mechanisms for implementing improvements in the animal drug approval process. Following passage of AGDUFA, an Office of New Animal Drug Evaluation Generics Working Group wrote draft proposed regulations for implementation of the generic act. The goal for FY 2009 is to publish notice of the proposed rule.

CVM during FY 2008 issued a large number of guidance documents to assist industry sponsors. For additional information on these publications, see Appendix A. The documents CVM issued included five new guidances providing information relevant to the approval and marketing of new animal drugs, eight revised guidances concerning approval requirements and processes, and two joint Agency guidances on the subject of processing standards. To improve the efficiency of the review process, we issued nine new Standard Operating Procedures (SOPs) to guide reviewers, and 11 revised SOPs for use by reviewers.

Actions to Improve the Efficiency of the Review Process

Implementing a system to improve business practices. The Office of New Animal Drug Evaluation is an Agency leader in business process innovation and improvement. The Office was recognized during the year as a model of best practices for the Agency that yield demonstrable performance and efficiency improvements. This included annual planning, quarterly evaluation reviews of work progress and cost, implementation of quality systems, and internal quality assurance audits.

In preparation for implementation of the end review amendment provision of ADUFA II, the Office of New Animal Drug Evaluation during FY 2008 developed internal standard operating procedures and conducted office-wide training for reviewers. The Office also revised its process for writing policies and procedures, to increase the efficiency and effectiveness of the process. These and other measures will allow more efficient and effective use of resources in completing the evaluation of new animal drugs, accelerating the time to regulatory decisions and/or approvals.

Office of New Animal Drug Evaluation Leadership Development Program. This program, developed during the year, provides a mechanism for communicating current leadership opportunities from across FDA to Office of New Animal Drug Evaluation employees. A wide range of accomplishments included developing a mentoring program; providing leadership development resources; and providing leadership opportunities to all members of the Office of New Animal Drug Evaluation to enhance leadership skill development and to develop candidates for succession planning.

Question Based Review. During the year, we initiated communication with the animal health industry to increase the quality of animal drugs submitted for evaluation/approval by using the Question Based Review format for guidance and implementing Quality by Design standards. These standards are derived from the FDA initiative “Pharmaceutical Quality for the 21st Century – A Risked Based Approach.” This action should enhance the level of public health protection by encouraging the industry to adopt the concept of better quality products with potential reduction in regulatory oversight. We anticipate significant implementation of this initiative during FY 2009.

RESEARCH TO SUPPORT ANIMAL DRUG REVIEW

Drug sponsors are responsible for submitting studies to prove that their drugs are safe and effective. Complementary work – accomplished by CVM, its contractors, and collaborators – may in the future alter or reduce the type and number of studies required for pprovals, thus improving the efficiency of the drug approval process.

FDA’s Critical Path Initiative has added a new dimension to this complementary work. During FY 2008, CVM scientists initiated several Critical Path studies, in collaboration with other FDA Centers, aimed at providing toolkits that will improve the efficiency of the animal drug approval process.

One investigation is a pharmacogenomic8 study to explore the potential impact of a multi-drug resistance-1 (MDR-1) gene mutation on drug safety and effectiveness in dogs, and to develop alternative test models in place of dogs. A mutation in the MDR-1 gene is known to occur in certain dog breeds. This mutation can alter the absorption, distribution, and excretion of certain drugs, thus resulting in life threatening toxicity from use of the drugs. Currently, safety studies required by the drug approval process are conducted in dogs that possess the MDR-1 mutant gene. Due to a diminishing number of available dogs, it is becoming difficult for drug sponsors to obtain the dogs needed to conduct the required studies. This Critical Path study aims to develop an in vitro method to identify possible substances that could be toxic to dogs possessing the MDR-1 gene, with the hope of developing an alternative animal model for conducting toxicity tests. This alternative model may eliminate the need to conduct safety studies in dogs.

The objective of the second study is to characterize and evaluate bronchial antimicrobial peptides using an animal pneumonia model. Information gained from the study will provide CVM with enhanced knowledge regarding the origin and cause of respiratory disease and host-drug interactions in response to infections. Antimicrobial peptides are short proteins that possess direct antimicrobial activity. Antimicrobial peptides for clinical applications are being developed in human therapeutics, and we anticipate that veterinary applications will follow soon. In addition to the evaluation of peptide activity, toxicity, and effectiveness/clinical performance, we will also need to be prepared to evaluate such basic issues as dosage form and delivery mode, as well the other standard parameters such as Minimal Inhibitory Concentration (MIC)/break-point determination. In addition to the therapeutic applications of these peptides, antimicrobial peptides may also have great utility as biomarkers of infection or inflammation, or as surrogates in the evaluation of disease progression or response to treatment with more conventional antimicrobial agents. We believe that evaluation of these compounds in animal models will shed some light on their use both in humans and animals.9

Manufacturing Facility Visits Enhance Review Process

During the past year, reviewers from the Division of Manufacturing Technologies visited two animal drug manufacturing facilities, each of which specializes in a different aspect of animal health. The goals of these visits were to provide firsthand perspectives of the manufacturing processes for different dosage forms, to educate Division of Manufacturing Technologies reviewers about some of the challenges that industry faces on a daily basis and to facilitate the sharing of information by opening new channels of communication. The group learned about the production of medicated feeds, observing the production of a Type A Medicated Article. Then they followed the life cycle of a medicated feed from blending for production of Type B and C feeds through to on-site mixing of feed rations for cattle. The group also visited a pharmaceutical facility that produces a variety of dosage form drugs for animal and human use, including sterile and nonsterile liquids, tablets, and pastes. They toured the manufacturing floor, observing the filling of sterile and nonsterile containers, the production of tablets, and the packaging process. They also toured quality control chemistry and microbiology laboratories.

These visits allowed our reviewers to see how the manufacturing processes work and how facilities are laid out, neither of which can be learned from the sponsors’ submissions alone. Better process understanding along with improved working relationships will facilitate the goal of one-cycle review for animal drug approval.

Protecting the Health of Companion Animals

THE CHALLENGE

The increasing companion animal population in the United States, along with the affinity that pet owners have for their pets – evidenced by rising expenditures for pet care and aggressive marketing of pet products – illustrate the need for more safe and effective drugs for prevention, treatment and control of diseases in companion animals, and for protecting the integrity of the pet food supply.

FY 2008 ACCOMPLISHMENTS

During the year we undertook comprehensive follow-ups to the episodes of pet food contamination that occurred during the previous fiscal year, guided by the FDA’s Food Protection Plan and provisions of the Food and Drug Administration Amendments Act of 2007 (FDAAA). In addition, we approved several significant New Animal Drug Applications and supplements for companion animal drugs. We also approved new labeling to strengthen product safety for the return to the market of a drug used to prevent heartworm disease in dogs. The following subsections detail our accomplishments.

PET FOOD CHALLENGES AND ACCOMPLISHMENTS: THE MELAMINE AFTERMATH

The Congressional Mandate

Following the melamine incident associated with pet food and several contamination episodes involving human food, FDA adopted the Food Protection Plan in November 2007. That same month, Congress under the FDAAA required FDA to take steps designed to improve the safety of pet food and ingredients.

FDAAA requires FDA to establish:

  • Ingredient standards and definitions, processing standards, and labeling standards—including nutritional and ingredient information—for pet food.
  • An Early Warning Surveillance and Notification System to identify adulteration of the pet food supply and illness outbreaks, and to notify veterinarians and other stakeholders of pet food recalls.
  • A searchable database of recalled pet foods to ensure efficient and effective communications during recalls.
  • A “Reportable Food Registry” for all animal food including pet food. Reportable food is any food that carries a reasonable probability that its use or exposure to it will cause serious adverse health consequences or death to humans or animals.

The Agency and CVM Response

Ingredient, processing, and labeling standards for pet foods. The Agency issued a request for public comments in April 2008, and CVM held a public meeting in May 2008, in part to obtain input on processing and ingredient standards and on the labeling for pet food. CVM used information from the meeting and comments in developing draft pet food labeling regulations and in developing processing standards for animal feed. The draft pet food regulations were in Agency clearance at the end of the fiscal year. We are also developing ingredient standards regulations.

Enhanced Federal regulations for the labeling of pet food will improve the safety of the product, and improve consumer understanding of the contents and nutritional value. Processing standards for all segments of the animal feed industry, including the pet food industry, will improve the safety and uniformity of animal feeds and will directly impact and improve the safety of animal derived products for human consumption.

Early Warning Surveillance and Notification System. We have identified and are utilizing an early warning surveillance system and notification for recalls that includes pet food. Among other responses, we are better utilizing data “mining” and epidemiology to identify and respond to outbreaks as early as possible. The improved utilization and refinement of the early warning surveillance system will enhance our ability to detect problems earlier, improve notification to all stakeholders, limit the spread and impact of the problem, and improve FDA’s and industry’s ability to recall the affected products.

CVM is planning a meeting to discuss the development and implementation of the “Pet Event Tracking Network,” including development of a database and models for incident reporting and investigation. The Pet Event Tracking Network is a concept proposed by veterinarians, animal feed regulators, and others involved with animal health issues during the 50-State Gateway to Food Protection Meeting held in August 2008. The Pet Event Tracking Network would be an early warning system to report contamination incidents concerning pet food.10  At present, the United States does not have an organized system, voluntary or required, for early reporting of pet food problems. The proposed system would be supported by adequate laboratory facilities and an established mechanism for conducting national epidemiological investigations of foodborne outbreaks involving companion animals.

Reportable Food Registry. We are working with the Center for Food Safety and Applied Nutrition to identify animal foods, including pet foods, that have a reasonable risk of causing serious injury to animals and humans.

Detecting Melamine Residues in Animal Feed and Human Food

As the melamine crisis unfolded during 2007, there was an immediate need to develop methods to detect the adulterants (melamine and related analogs) in animal feed and in tissues of animals produced for human consumption. CVM researchers responded by conducting a study that provided tissues for chemists developing methods to detect melamine. They also evaluated the development of crystals and their chemical composition in pigs, fish, chickens, and a cat. A paper describing the emergency response to the pet food recall and the study was prepared and published in FY 2008.11

A second article describing the tissue methods developed for melamine and cyanuric acid was also published in FY 200812, and a third article on the same subject was accepted for publication.

Detecting melamine and cyanuric acid in animal feeds – application to infant formula. In 2008, CVM scientists developed a method for the detection of melamine and cyanuric acid in animal feeds. The availability of this completed method had a crucial role in the Agency’s quick response to the discovery in September 2008 that melamine was being used to adulterate milk and infant formula in China. During the initial discussions of the problem, the CVM researchers recognized that the feed method likely would be suitable for testing milk products and provided the completed method to scientists in the FDA Office of Regulatory Affairs. Working collaboratively, the Office of Regulatory Affairs and CVM scientists in a matter of days demonstrated that the method could be adapted directly as written for use in testing infant formula. The Office of Regulatory Affairs scientists immediately began to validate the method for infant formula. Within a month, the Agency had a fully tested method for use in FDA regulatory laboratories, and made the method available (on the Web site of FDA’s Center for Food Safety and Applied Nutrition) for use both by regulatory agencies and industry worldwide for the determination of melamine and cyanuric acid in infant formula. Availability of the method provided assurance to the public that, if a suspect product was found in the United States, FDA could test it for melamine.

Detecting melamine and cyanuric acid in fish. In 2008, CVM researchers initiated a depletion study in trout and catfish to evaluate tissue levels of melamine, cyanuric acid, and a combination of the two triazines. This study is providing important information to the Agency on expected excretion rates of these substances in aquatic organisms, which will help ensure the safety of the food supply. Additional studies examining the threshold doses needed to induce crystals and the effects of sequential administration of triazines were ongoing at the end of the fiscal year.

Award Nomination - Dr. Renate Reimschuessel, Service to America Medal finalist

For her work to uncover properties of melamine and related chemicals in pet food that were so dangerous to dogs and cats, CVM scientist Dr. Renate Reimschuessel was named in June 2008 as one of 29 “Service to America Medal” finalists and was a contender for one of the eight medals that were awarded in September 2008. The medals were awarded by the Partnership for Public Service, which awards the medals to Federal employees who make significant contributions to the safety, health, and wellbeing of American citizens.

Dr. Reimschuessel is a research biologist at CVM’s Office of Research. Through her efforts, the Food and Drug Administration was able to determine how melamine and related chemicals were responsible for kidney damage in dogs and cats.

Although Dr. Reimschuessel was not selected as one of the medalists, her nomination reflects the significance of her achievements.

COMPANION ANIMAL DRUG CHALLENGES AND ACCOMPLISHMENTS

Drug Approvals

CVM approved several significant original and supplemental New Animal Drug Applications for companion animals in fiscal year 2008:

CONVENIA (cefovecin), a new chemical entity, is an antimicrobial for use in dogs and cats. It is an injectable product approved for the treatment of skin infections (wounds and abscesses) caused by susceptible strains of Pasteurella multocida in cats; and the treatment of skin infections (secondary superficial pyoderma, abscesses, and wounds) caused by susceptible strains of Staphylococcus intermedius and Streptococcus canis (Group G) in dogs.

VETSULIN (porcine insulin zinc) is the first approved insulin for cats. It is approved for reduction of hyperglycemia and hyperglycemia-associated clinical signs in cats with diabetes mellitus.

The Return of PROHEART 6 to the Market

During the year, CVM announced the return to the market of PROHEART 6 (moxidectin) Sustained Release Injectable for Dogs, under a strengthened risk minimization and restricted distribution program. The novel risk management program is designed to enhance the safe use of the heartworm preventive while minimizing the risk to the patient.

After the drug was voluntarily recalled in September 2004, following reports of adverse reactions, the manufacturer (Fort Dodge Animal Health) conducted studies to evaluate further the safety profile of PROHEART 6 and to investigate the reported adverse events. These studies included additional toxicologic and pharmacologic evaluations, which suggested the potential allergenic nature of some of the residual solvents that are utilized in the manufacture of PROHEART 6. As a result, Fort Dodge changed the process specifications for the active ingredient (moxidectin) in PROHEART 6 and marketed the product with the revised process in international markets, where there has been a decline in adverse event reports. The results of the toxicologic studies coupled with the lower adverse event frequency in international markets were factors in FDA’s decision to approve revised labeling and concur with Fort Dodge’s restricted return of PROHEART 6 to the U.S. market under the risk minimization plan. The program allows veterinarians to weigh the risk of heartworm disease in their patients with the benefits of using the drug, thus maximizing the benefits of heartworm protection, while minimizing the risk to dogs.

In addition to the plan, the PROHEART 6 label and Client Information Sheet have been revised, based on post-approval experience, to include updated safety information. Fort Dodge is implementing an educational and communication program that will require veterinarians to register with Fort Dodge and complete in-depth training as a condition of purchasing PROHEART 6.

CVM has received favorable feedback on the plan since the return of the product to the market. The success of the program is important to veterinarians and their clients, because PROHEART 6 is currently the only FDA approved heartworm preventive injectable that is effective for 6 months.

Increasing Drug Availability for Aquaculture and Other Minor Uses and Minor Species

THE CHALLENGE

The Minor Use and Minor Species Animal Health Act of 2004 (MUMS Act) challenges CVM to implement measures that will significantly expand the availability of drugs for minor uses and minor species. Because the potential sales volume is low, animal drug manufacturers lack economic incentive to seek animal drug approvals for minor uses (diseases that are rare in major species13) or minor species.14 The need in aquaculture is a good example. While fish are susceptible to their own set of diseases, the number and type of drugs approved for such indications are extremely small in comparison to the drugs that are approved and available for use in major species.

FY 2008 ACCOMPLISHMENTS

As described in the following paragraphs, CVM made considerable progress during the year in adopting new regulatory procedures and approving drugs to increase the availability of animal drugs for the treatment of minor animal species and uncommon diseases in major animal species. The accomplishments included adopting final regulations that provide for the marketing of unapproved drugs under certain conditions, and completion of several first-time drug approvals for use in minor species.

REGULATIONS IMPLEMENTING MUMS

Indexing Regulations

FDA in December 2007 adopted final regulations titled “Index of Legally Marketed Unapproved New Animal Drugs for Minor Species.” These regulations describe administrative procedures and criteria for index listing of a new animal drug for use in a minor species. A drug listed in the Index can be marketed legally without an approved application under the conditions specified in the Index listing. In general, the Index is limited to drugs for use in nonfood-producing minor species, with a limited exception for certain early life stages of food animals, such as some fish eggs.

The Index is intended to allow companies to legally market veterinary drugs for minor species for which there are no human food safety concerns without having to go through the long and expensive process of a new animal drug approval. Inclusion of a drug in the Index will largely be based on the evaluation of the target animal safety and effectiveness of each specific product by a panel of qualified experts.

The final regulations describe the process FDA will use to determine whether a new animal drug can be added to the Index. The procedures include sponsor submission of a request for eligibility, selection of the expert panel to consider the target animal safety and effectiveness of the new animal drug, and submission of the panel’s findings to the Agency for consideration in support of a request to add a drug to the Index.

Definition of Small Number of Animals

In March 2008, FDA issued a Notice of Proposed Rule Making defining “small number of animals” for designation of drugs for minor use in each of the seven major species. The Designation provision of the MUMS Act provides incentives to animal drug sponsors to encourage drug development and approval for minor species and for minor uses in major animal species. MUMS Act Designation of a new animal drug allows the drug sponsor 7 years of exclusive marketing rights to encourage the development of these limited demand drugs. The Designation provision applies both to drugs for minor use (in major species) and for use in minor species. The Designation provision of the MUMS Act includes a definition for the term “minor use” that relies on the phrase “small number of animals” to characterize such use. In response to Congress’ charge to the Agency to further define minor use, the notice proposes a definition for the term “small number of animals” that includes a specific threshold number of animals.

Although the “small number of animals” definition regulation was in the proposal stage, FDA used these criteria on a case-by-case basis during the fiscal year to designate its first minor uses in major species. We used these minor use criteria for the Designation of trilostane for the treatment of hyperadrenocorticism due to adrenocortical tumor in dogs. The Designation list can be viewed on the CVM Web site.

DRUG APPROVALS

Oxytetracycline for Two Aquaculture Indications

In July 2008, CVM approved TERRAMYCIN 200 for Fish (oxytetracycline dihydrate) Type A medicated article for two indications: (1) the control of mortality in freshwater-reared salmonids15 due to coldwater disease caused by Flavobacterium psychrophilum and (2) the control of mortality in freshwater-reared Oncorhynchus mykiss16 due to columnaris disease associated with Flavobacterium columnare. Besides adding the two new indications, the approval removes the temperature limitation on previously approved salmonid indications, which restricted the drug’s use to water temperatures above 48.2oF(9oC).

TERRAMYCIN 200 for Fish is the first drug approved for the control of mortality due to systemic columnaris disease associated with Flavobacterium columnare in freshwater-reared Oncorhynchus mykiss. Columnaris can be a problem for trout and other fish when water temperatures are above 57oF (14oC). TERRAMYCIN 200 for Fish is also the second drug approved for use during outbreaks of coldwater disease in salmonids. Untreated, this disease can cause significant losses among salmonids at State and Federal hatcheries including native species in restoration programs. The drug is Designated under MUMS Act regulations for the systemic columnaris and coldwater disease indications.

As part of the human food safety requirements for approval, we reviewed TERRAMYCIN 200 for Fish under CVM’s Guidance for Industry #152 “Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern.” That guidance provides a regulatory pathway sponsors can use to show how any antimicrobial resistance risks associated with the use of an antimicrobial drug in food-producing animals can be managed without endangering public health.

New Antimicrobial for Salmonids for Treatment of Furunculosis

In November 2007, CVM approved AQUAFLOR (florfenicol) Type A medicated article for the control of mortality in freshwater-reared salmonids due to furunculosis associated with Aeromonas salmonicida. AQUAFLOR is the first new antimicrobial approved for use during furunculosis outbreaks in more than 20 years.

Furunculosis is a serious salmonid pathogen that can appear as an acute septicemic infection. The disease causes significant losses of hatchery-reared salmonids, including losses at State and Federal hatcheries producing fish for native species restoration programs.

AQUAFLOR is a Veterinary Feed Directive drug, which means that the medicated feed can be fed only on the order of a licensed veterinarian. Veterinary Feed Directive status also means that the extralabel or off label use of medicated feed containing the drug is not allowed. AQUAFLOR, as approved for furunculosis, is a Designated drug under MUMS.

Albendazole for Goats

In January 2008, CVM approved VALBAZEN (albendazole) 11.36% suspension for the treatment of adult liver flukes (Fasciola hepatica) in non-lactating goats. This is the first approval for this indication in goats. This supplemental NADA relied on public master file data compiled under the National Research Support Project #7, a national agricultural research program for obtaining clearances for use of new drugs in minor animal species and for special uses. The approval is a Designated drug under the MUMS Act regulations.

RESEARCH TO SUPPORT DRUG APPROVALS

Antimicrobial Susceptibility Testing

CVM scientists during FY 2008 evaluated the susceptibility of bacteria in the intestines of tilapia after feeding oxytetracycline to the fish. Most isolates of Bacillus cereus, bacteria normally found in the intestines of tilapia, are susceptible to oxytetracycline when the fish have been fed unmedicated aquaculture feeds. After oxytetracycline-medicated feed is administered, though, some of the isolates are resistant to oxytetracycline. To ensure the continued effectiveness of oxytetracycline drugs, we wanted to find out why this resistance happens and how rapidly it occurs.

During the weeks prior to administration of oxytetracycline, the B. cereus isolates obtained from the tilapia feces had a susceptible phenotype. During and immediately after treating with oxytetracycline medicated feed, we found that most of the bacteria isolated from the feces were resistant to oxytetracycline. After an additional 8 weeks following administration of the drug, most of the bacteria were again susceptible to oxytetracycline. We needed to determine if the bacteria were changing their susceptibility patterns after exposure to oxytetracycline, or if there were changes in the proportions of different populations of bacteria (i.e., more susceptible bacteria were growing again after the antibiotic was no longer present).

To find out, we examined the Pulse Field Electrophoretic (DNA fingerprint) patterns of B. cereus from the feces of fish before, during, and after feeding medicated feed. We found that there are primarily three different populations of B. cereus that express either susceptible or resistant phenotypes; the susceptibility patterns did not change within the population, but instead relative numbers of colonies in those populations changed during antimicrobial therapy.

These results indicate that there is not a conversion of susceptible bacteria to resistant “super bugs,” but instead that the antibiotic kills off the susceptible bacteria; the susceptible bacteria return after the treatment. This finding would indicate that there is less chance of causing alterations in susceptibility of normal microflora in fish when oxytetracycline is administered.

Pharmacokinetics in Minor Species

CVM researchers during FY 2008 conducted studies to evaluate pharmacokinetic parameters of two formulations of oxytetracycline fed to rainbow trout for 10 days. We found that both formulations of oxytetracycline had similar serum blood values. We measured serum concentrations using a microbiological assay to determine biologically active concentrations, and high-performance liquid chromatography (HPLC) to determine chemically detectable concentrations.

This study determined the elimination half-life of oxytetracycline in rainbow trout held at specified water temperatures. At the end of the fiscal year, we were preparing a publication to report these findings. These data will be useful as we begin to develop interpretive criteria for susceptibility results of oxytetracycline for fish pathogens. In other words, we will try to predict whether a drug will work successfully to treat fish diseases based on the concentrations required to kill the pathogen and the concentrations achievable in the fish’s body.

Reducing Risk from Antimicrobial Resistance

THE CHALLENGE

Scientific evidence demonstrates that the use of antimicrobial drugs in food-producing animals can result in the selection of resistant bacteria. Resistant foodborne bacteria can then be transferred to humans, resulting in illness. If the patient needs antimicrobial drug treatment, that therapy may be compromised because the drugs of choice may be ineffective. CVM’s challenge is to develop policies and programs that reduce the risk to human health from the use of antimicrobial drugs of human-health significance in food-producing animals.

FY 2008 ACCOMPLISHMENTS

In cooperation with other agencies, CVM has undertaken proactive surveillance, research, education, risk assessment, and risk management programs to reduce risks to human health that can result from the use of antimicrobials in food-producing animals. We achieved significant progress in these efforts during the past year, responding to FDA strategic goals and Departmental objectives.

MONITORING FOR DEVELOPMENT OF RESISTANCE

National Antimicrobial Resistance Monitoring System (NARMS)

CVM leads the NARMS, established more than a decade ago as a collaborative effort between CVM, the U.S. Department of Agriculture, and the Centers for Disease Control and Prevention. The NARMS program monitors select enteric bacteria from humans, animals, and retail meats for changes in susceptibility to a panel of antimicrobial drugs important in human and animal medicine. The ultimate goal of these activities is to prolong the lifespan of approved drugs by promoting prudent and judicious use of antimicrobial drugs in food-producing animals and to identify areas for more detailed investigation.

Dr. Patrick McDermott serves as the NARMS Acting Director, as well as the Acting Director of the Division of Animal and Food Microbiology, and Dr. Beth Karp is the NARMS Coordinator. Both are with CVM’s Office of Research. Dr. Karp’s responsibilities include coordination of the epidemiological activities of all three arms of the NARMS program – animal (administered by the U.S. Department of Agriculture), human (administered by the Centers for Disease Control and Prevention), and retail meat (administered by FDA) – as well as the development of the annual Executive Report. Much of the NARMS activity involves collaborative efforts, not only between Federal agencies but also with academic institutions and within FDA.

Web Site and Data Reporting. We have seen steady progress in the timeliness and development of user-friendly features of the NARMS reporting, with the latest published Executive Report featuring interactive tables. The 2006 NARMS Retail Meat Annual Report was published shortly after the end of FY 2008, and the 2007 report was scheduled for publication early in calendar year 2009. (The 2005 NARMS Executive Report was published in early 2009.) NARMS reports are available at http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistanceMonitoringSystem/ ucm093532.htm.

In addition to these annual reports, NARMS also generates periodic publications with useful information related to resistance issues. For example, NARMS scientists during the year completed a report on the prevalence, antimicrobial susceptibility, and genetic relatedness of Salmonella serovar Heidelberg isolates from retail meats across the United States. Salmonella serovar17 Heidelberg is among the most frequently isolated serovars, both in clinical cases of salmonellosis and from retail meats and food animals in the United States and Canada (it is a major serovar only in those two nations). The occurrence of antimicrobial resistance in Salmonella serovar Heidelberg is particularly serious because of the propensity of this serovar to produce severe extra-intestinal infections.

All of the published information will help meet the FDA Strategic Plan and Food Protection Plan objectives to detect safety problems earlier and target interventions more accurately to prevent harm to consumers.

Science Board Review. FDA NARMS personnel met twice with Federal partners (the U.S. Department of Agriculture and the Centers for Disease Control and Prevention) in FY 2008 to develop strategic approaches for implementing recommendations made during FY 2007 by a Subcommittee of the FDA Science Board. One of the meetings was in September 2008, when NARMS partners met to seek ways to harmonize databases and share access, evaluate laboratory methods, and overcome limitations in sampling.

International Activities

CVM actively participated during the year in the ad hoc Intergovernmental Task Force on Antimicrobial Resistance (TFAMR) of the Codex Alimentarius Commission. CVM leads the U.S. Delegation to the TFAMR; Dr. David White, the acting Director of the Office of Research is the U.S. Delegate, and others from CVM (Dr. Merton Smith, Dr. Barry Hooberman, Dr. Donald Prater, and Dr. Steve Yan) contribute leadership, expertise, and coordination to the U.S. delegation. The United States, under Dr. White’s leadership, is chairing a working group to harmonize drafts on risk assessment, risk profiles, and risk management.

The work of the TFAMR will result in internationally recognized guidance that national governments will be able to use to appropriately assess and manage the risk from antimicrobial resistance that may occur as a result of the use of antimicrobial drugs in veterinary medicine. Such guidance is essential so that the regulation of use of antimicrobials in food-producing animals will be based on a rational approach that uses objective evidence to determine degree of risk.

CVM scientists participated in the World Health Organization Global Salmonella Surveillance (WHO-GSS) program by taking part in the Annual WHO-GSS planning meeting and national professional meetings on food safety. In addition, during the year CVM continued to provide resources for training scientists in numerous countries in laboratory-based surveillance of foodborne pathogens. These efforts will enhance capacities beyond our borders to monitor the prevalence and antibiotic resistance of foodborne pathogens.

PRE-APPROVAL AND POST-APPROVAL REVIEW FOR ANTIMICROBIAL RESISTANCE

Under the leadership of the Office of New Animal Drug Evaluation, we continued the strategic implementation of Guidance for Industry (GFI) #152, “Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern,” for evaluating critically important and highly important antimicrobials emphasizing risk mitigation, communication, and refined release assessment. (Under GFI 152, we rate antimicrobials important, highly important, or critically important based on the probability that human exposure to resistant bacteria would result in an adverse health consequence). We helped some 18 different drug sponsors of approximately 35 different compounds consider how microbial food safety information can be used to specify conditions of use that will not adversely impact public health.

RESEARCH TO SUPPORT ANTIMICROBIAL RESISTANCE SURVEILLANCE AND REGULATION

Developing Rapid Screening Methods

CVM scientists during the year completed a collaboration with scientists from the Max Planck Institute for Infection Biology to investigate the emergence of antimicrobial resistance phenotypes and evolutionary relatedness of veterinary diagnostic and retail meat isolates of Salmonella enterica serovar Newport. We used novel DNA fingerprinting techniques in conducting this investigation. This study demonstrated that recent multidrug-resistant isolates are derived from a lineage distinct from those historically found in the United States, and may indicate that this strain was recently introduced into the country.

Resistant Pathogens

CVM scientists during the year conducted studies in partnership with researchers at North Carolina State University and The Ohio State University to catalog the extent of antimicrobial resistance genes in enteric foodborne bacteria from the field and from the NARMS program. We are using a novel microarray method developed in CVM’s Office of Research to analyze antimicrobial-resistant bacterial isolates. Early results suggest that bacteria often carry resistance genes that are not functional. Once the microarray method is refined, it will be used routinely to characterize the genetic content of NARMS isolates.

Microbial Virulence

Most E. coli are harmless, but some are pathogenic and can cause enteric or extra-intestinal infections in humans. Human E. coli enteritis is often transmitted through consumption of contaminated food, especially products derived from animals. Shiga-toxin-producing E. coli (STEC) and enterotoxigenic E. coli (ETEC) are the groups of foodborne pathogenic E. coli that are of highest concern. Little is known about the actual prevalence of pathogenic E. coli in retail meats, in part due to the lack of routine screening of these pathogens in foods. The objective of a study conducted during the fiscal year by CVM scientists is to screen for ETEC, STEC, and other pathogenic E. coli among isolates recovered from retail meat samples collected for NARMS. The purposes are to determine the prevalence of these pathogens and assess the potential risk of foodborne E. coli infections. Preliminary data suggest the incidence of pathogenic E. coli in meats is very low (less than 1 percent).

NARMS researchers at the Office of Research, in collaboration with scientists from the FDA Center for Food Safety and Applied Nutrition, the University of Minnesota, and the University of Maryland, are completing a study of Salmonella serovar Kentucky from humans, animals, and meats. The study is aimed at better understanding the features of this organism that explain its low pathogenic potential.

CVM collaborated during the year with University of Maryland scientists to understand the potential virulence of Campylobacter by characterizing the elaboration of inflammatory mediators in cultured epithelial cells exposed to bacteria. Because different strains have different pathogenic potentials, this research can help FDA to evaluate the public health hazard posed by the presence of Campylobacter in foods.

Identifying a Pathogenic Gene

STEC E. coli are foodborne pathogens. There is considerable variation in the genes for toxin type 2 (Stx2) produced by STEC. One such Stx2 variant, Stx2dact, is associated with increased disease severity. With collaborators at the University of Maryland, we found that certain STEC isolates from food, animals, and humans carried the Stx2dact gene. This was the first report of this pathogenic variant in foods and animals, and it lays the foundation for monitoring this strain type in the food supply.

Basic Research in the Genetic Mechanisms of Antimicrobial Resistance

The horizontal acquisition of resistance genes, such as integrons, is central to antimicrobial resistance development in bacteria. Increased genetic mutation frequencies may reduce barriers to interspecies genetic exchange and, therefore, may be important in the acquisition of mobile resistance determinants. To explore this phenomenon, NARMS personnel in the Office of Research worked with colleagues at the Center for Food Safety and Applied Nutrition and the University of Maryland to examine the role played by mutation repair mechanisms in the emergence and spread of antibiotic resistance on integrons.

The study showed that a specific integron, in combination with Salmonella Genomic Island 1, plays an important role in antimicrobial resistance dissemination, and that defective mutation repair systems did not play a major role.

PFGE Enhancement

NARMS scientists working with collaborators at the Center for Food Safety and Applied Nutrition, the University of Maryland, and Northwest A & F University in China showed that the discriminatory power of pulsed-field gel electrophoresis (PFGE) could be substantially improved by addition of a third DNA restriction enzyme. This innovation permitted the differentiation of strain from four serovars that previously could not be distinguished. Application of these findings will make PFGE more informative for source tracking and outbreak investigations of these four serovars and other Salmonella pathogens.

Molecular Diagnostic Assays for Detecting Genes of Biomedical Importance

CVM scientists recently collaborated with Center for Food Safety and Applied Nutrition researchers and investigators from the J. Craig Venter Institute (formerly The Institute for Genomic Research) in sequencing the genomes of 17 strains representing 12 Salmonella serovars of public health importance. The strains chosen for genomic18 analysis were selected based on an extensive examination of their potential to provide information needed for examining pathogenicity, transmission, origin, ecology, evolution, and dissemination of antimicrobial resistance. The majority of the strains chosen for sequencing originated from the NARMS program and included susceptible and multidrug resistant variants. The sequences were completed during the fiscal year, and gene identification and labeling should be finished early in FY 2009. The results of this work will lead to rapid molecular diagnostic assays for detecting genes of biomedical importance, including genes that are potential virulence determinants. The results will also guide anti-infective therapy, and provide a means to rapidly characterize field strains in support of animal and public health epidemiology.

Controlling Risk from BSE

THE CHALLENGE

BSE is a chronic, degenerative, always fatal neurological disease affecting the central nervous system of cattle. BSE belongs to a family of diseases known as transmissible spongiform encephalopathies that include several ruminant and nonruminant animal diseases. Laboratory and epidemiological evidence strongly suggests that people can contract a human transmissible spongiform encephalopathy, variant Cruetzfeldt-Jakob Disease, by consuming meat products derived from BSE-infected cattle. In the absence of adequate controls, BSE could spread among the cattle population through feed ingredients derived from infected cattle.

FY 2008 ACCOMPLISHMENTS

Much of our effort to combat BSE in 2008 focused on enforcing and strengthening our BSE feed regulation, which prohibits the use of certain mammalian-origin proteins in ruminant feed. A major initiative involved an amendment of the BSE feed rule to strengthen public health protection. The goal is to prevent the establishment and amplification of BSE in the United States through animal feed. Following are highlights of some of our achievements that accomplished FDA’s strategic goal of consumer protection, and the Department-wide objective of improving the safety of food products.

U.S. AND WORLDWIDE BSE DETECTION

As in the previous fiscal year, FY 2008 did not see the discovery of any BSE-infected cattle in the United States. During the same time period, four new BSE cases were detected in Canada. Worldwide, the incidence of BSE continued to decline significantly.

STRENGTHENING THE BSE FEED REGULATION

Overview of Rule Revision

FDA’s 1997 BSE feed rule prohibits the use of mammalian-origin proteins in feed fed to ruminants,19 while allowing the use of these materials in feed for non-ruminant animals.20 In April 2008, the Agency revised the regulation to strengthen further the feed-related safeguards against BSE in the United States. The revised rule prohibits the use of the highest risk cattle materials in the food or feed of all animals, ruminants and non-ruminants, including pet food.

Need for Revision

Compliance with the 1997 rule has been extremely high. No cases of BSE in animals born after the introduction of the ban have been detected, and no new BSE cases have been reported in the United States since March 2006. Nevertheless, the FDA concluded that additional protections were needed. One reason was that inspections of feed manufacturing firms had identified a small number of instances of inadequate cleanout procedures, mislabeling, and recordkeeping deficiencies. Although few in number, such lapses could allow food and feed intended for nonruminants to get into the food supply for ruminants. In addition, the amount of feed material needed to transmit the disease is so small that it is possible that the procedures followed by a seemingly compliant firm may not be sufficiently robust to prevent cross-contamination of cattle feed with enough infectious material to cause new cases of BSE. This scenario best explains why cases of BSE continued to be found in cattle born in the United Kingdom after implementation of that country’s ruminant-to-ruminant feed ban.

Details of the Revised Rule

The new rule is intended to mitigate compliance failures and prevent the potential transmission of the BSE agent through cross-contamination or on-farm misfeeding of prohibited material to ruminants. Thus, the new rule is expected to further reduce risk of any ruminant exposure to the BSE agent not eliminated by the 1997 feed rule.

Revisions to definition of prohibited material. Scientific data indicate that roughly 90 percent of BSE infectivity in cattle is contained in the brain and spinal cord of older cattle.21 For this reason, the new rule focuses primarily on removing the brains and spinal cords of older cattle from all animal feed. Specifically, the new rule prohibits the use of the following cattle materials in the food or feed of all animals, including pet food:

  • The entire carcass of BSE-positive cattle;
  • The brains and spinal cords from cattle 30 months of age and older;
  • The entire carcass of cattle not inspected and passed for human consumption that are 30 months of age or older and from which brains and spinal cords were not removed;
  • Tallow that is derived from BSE-positive cattle; tallow that is derived from other materials prohibited by this rule that contains more than 0.15 percent insoluble impurities; and
  • Mechanically separated beef that is derived from the materials prohibited by this rule.

We refer to these materials as “cattle materials prohibited in animal feed,” or CMPAF.

The final rule allows renderers to process the entire carcasses of dead stock cattle22 under 30 month of age for use in nonruminant feed. (The risk of BSE in cattle less than 30 months of age is considered to be exceedingly low.) The proposed rule would have required removal of the brain and spinal cord from all cattle, regardless of age, because of FDA concerns that government inspectors are not routinely available in rendering plants to verify the ages of dead cattle. The Agency changed the final rule, based on comments that age determination of dead stock cattle in the rendering plants is feasible. The regulation allows renderers the option of determining the age of the cattle and processing cattle under 30 months of age without removing the brain and spinal cord. However, the final rule requires renderers to develop and maintain written procedures for determining the age of and/or removing the brain and spinal cord from dead cattle.

FDA also based its proposal on European surveillance data that showed that cattle not inspected and passed for human consumption (dead stock) were included among the cattle at highest risk of BSE. However, the comments supported the conclusion that very little risk reduction is gained by excluding material from such cattle that are less than 30 months of age.

Inspections and record-keeping. During inspections at rendering facilities, FDA intends to verify that renderers maintain records sufficient to demonstrate that material rendered for use in animal feed does not contain CMPAF. In addition to written procedures for determining the age of cattle, the regulations also specify written procedures for effectively excluding the brain and spinal cord from animals 30 months of age and older. Investigators will be verifying that actual practices are effective in providing compliance with the regulation. The Agency revised the final rule to clarify that a renderer’s records must include certification from each supplier, or other documentation acceptable to FDA, that CMPAF has been excluded from materials to be rendered for use in animal feed.

Disposing of CMPAF. As a result of this final rule, a large volume of byproducts from the beef and cattle industries will no longer be allowed to be rendered for animal feed use. Alternative means of disposing of this material include landfill, composting, incineration, alkaline hydrolysis, and burial.

Country exception. In response to comments to the proposed rule, FDA revised the final rule so that the Agency may designate a country as not subject to the new requirements; that is, animal protein from the country would not have to have CMPAF removed if it is intended for consumption by nonruminant animals. Any country seeking such a designation must submit a written request to the Director of CVM, providing information about that country’s BSE case history, risk factors, measures to prevent the introduction and transmission of BSE, and any other information relevant to determining the country’s BSE status.

Conclusion

Two and a half years passed from the time of the proposed rule (October 2005) until publication of the final rule (April 2008). During that time, FDA reviewed more than 800 comments, including comments from industry, State and local governments, trade associations, academia, and consumers. Among other time-consuming steps, the Agency reviewed comments challenging FDA’s estimate of the cost of the new regulation. This review required an extensive reanalysis of the economic impact of the rule. We believe that the time and effort required, including that needed to draft changes to the proposed rule, were worthwhile. The revised regulation provides an additional margin of safety by reducing the consequences of inadvertent cross-contamination or on-farm misfeeding, thereby helping to ensure that the U.S. beef supply remains safe.

We plan to publish a Guidance for Industry to assist the industry in complying with the revised regulation. More information about BSE and the BSE rule is available on the CVM Web site at http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/ComplianceEnforcement/BovineSpongiformEncephalopathy.htm.

INTERNATIONAL INVOLVEMENT

We provided information to trading partners and the World Organisation for Animal Health that included feed ban enforcement data and updates on FDA’s science-based enhancements to animal feed controls for preventing transmission of BSE through feed.

A CVM staff member, Dr. Dragan Momcilovic, continued to serve as the only U.S. member of the Board of SAFEED-PAP,23 a European project that is aimed at the development of improved testing methods for detection of prohibited animal protein in feed. The participants, mostly regulatory scientists, include representatives of national laboratories and several universities. A large number of European nations, in addition to Japan, China, and the United States, participate in the project.

TRAINING, EDUCATION, AND ENFORCEMENT

We continued to train inspection personnel, so that the BSE feed rule will be enforced effectively and efficiently. We also continued to provide educational outreach to the regulated industry.

Specifically, during FY 2008 we conducted a formal, full-day training course for inspection personnel. We also provided training/outreach information to feed regulators and industry personnel at a number of other meetings. CVM will increase training activities in FY 2009 to ensure proper training for inspectors for the implementation of the 2008 amendment to the BSE rule.

Additionally, we provided updates on BSE inspections and enforcement, as well as information about the new BSE rule, at several meetings sponsored by the Association of American Feed Control Officials; two of the workshops were open to industry representatives. We presented the same information at a meeting sponsored by FDA’s Division of Federal-State Relations for representatives of States that have contracts to do inspection work for FDA. We will continue educational outreach to industry during FY 2009 to help with compliance with the revised feed rule.

During FY 2008, the FDA district offices and State agencies conducted more than 7,889 inspections for BSE feed rule compliance at renderers, feed manufacturers, and other firms. More than 98 percent of the inspections were found to be NAI (no action indicated), meaning that the firms were in compliance. No firms were classified OAI (official action indicated); that is, no serious violations were found. We did classify approximately 0.8 percent of the inspections as VAI (voluntary action indicated). Typically VAI involves minor recordkeeping violations, which can be corrected at the time of the inspection. As a result, no formal enforcement actions (Warning Letters, injunctions, or seizures of violative products, for example) were taken during FY 2008.

DEVELOPING ANALYTICAL METHODS FOR DETECTING PROHIBITED PROTEIN

During the year, we completed peer validation of the real time polymerase chain reaction (PCR) method developed by CVM scientists to detect prohibited animal proteins in animal feed. The method will detect cattle, sheep, and goat materials produced under processing conditions used in the United States and European Union. The real time PCR method represents a significant improvement over the current PCR method, because a single analyst can analyze 12 samples in a little more than 2 hours. The current method requires 8 hours to analyze these same 12 samples. At the end of the fiscal year, we were working actively with the FDA field laboratories to transfer the method to those laboratories for use in surveillance and compliance activities. The process of transferring the method included training in the methodology prior to releasing it for use by the laboratories.

With the help of a visiting scientist, CVM scientists during the year were able to modify further the real-time PCR method into a multiplex real-time PCR method, which permits the detection of cattle, sheep, goat, deer, and elk in a single reaction tube. This test will also permit detection of ruminant proteins rendered in the European Union. One goal of this effort is to create an assay in which both the DNA extraction and PCR assay reagents are contained in two ready-to-use, commercially available kits. By having all the assay components ready to use from commercial kits, the FDA field laboratories will not need to make up any component, nor will they need to constantly conduct quality control checks of reagents that they need to prepare. Eliminating variation in reagents between different testing laboratories avoids a potential source of error when performing this method.

Avoiding Unsafe Drug Residues in Human Food

THE CHALLENGE

CVM is charged with ensuring that meat, poultry, seafood, and milk are safe from harmful veterinary drug residues, and that any such residues are within established tolerance. Firms or individuals who present for slaughter animals that are adulterated with illegal drug residues – identified through the U.S. Department of Agriculture’s National Drug Residue Monitoring Program – may cause a significant public health concern. Investigating violative residues, including residues from drugs prohibited from extralabel use in food animals and from residues of drugs not approved for food animal use, is a high priority for the Center.

FY 2008 ACCOMPLISHMENTS

The following summarizes our FY 2008 efforts to avoid unsafe drug residues in animal food products.

UPDATING REGULATORY METHODS USED IN RESIDUE TESTING

In collaboration with the U.S. Department of Agriculture’s Food Safety and Inspection Service, CVM during the year started an effort to bridge, validate, and update residue testing methods for drug residues found in animal tissues. This effort includes studies to bridge between selected approved regulatory methods that may be outdated and methods currently used by the Food Safety and Inspection Service to confirm the presence of residue.24

To get started on this task, CVM established a working group to identify existing resources and additional resource needs for the required studies.

The working group consists of members from CVM’s Office of New Animal Drug Evaluation, Office of Surveillance and Compliance, and Office of Research. The working group meets periodically with Food Safety and Inspection Service representatives for progress updates.

The first method being developed is for penicillin G in bovine tissues. CVM scientists are designing the method to allow for the addition of more drugs in the same test, i.e., multiresidue testing.

ENFORCEMENT TO CONTROL DRUG RESIDUES IN MEAT

In September 2008, FDA announced that a West Virginia cattle dealer had been sentenced to 6 months probation for refusing to obey court orders issued in 2006 and 2008 that prohibited the introduction of animals into the food supply until FDA had approved the dealer’s record-keeping system. FDA initiated the case after illegal levels of drug residue were found repeatedly in calves that the dealer sold for use as human food. The violations involved 23 positive tests for neomycin, penicillin, gentamicin, and other antibiotics. Under terms of the probation, the dealer was barred for 6 months from purchasing, selling, obtaining, or transferring any animals that may be used as human food. After that time period, the dealer is prohibited from these activities until FDA approves the dealer’s written record-keeping system.

During FY 2008, FDA issued more than 30 Warning Letters to dairies and farms that offered for sale animals as food that contained approved and unapproved drug residues in edible tissues in excess of FDA tolerance levels. FDA found that the animals were held under conditions that were inadequate so that medicated animals bearing potentially harmful drug residues were likely to enter the food supply. Many of the drugs were not used in conformance with the approved labeling and did not qualify for an exception to the general rule against extralabel uses. Under the Federal Food, Drug, and Cosmetic Act, “extralabel use,” i.e., the actual or intended use of an approved animal or human drug in an animal in a manner that is not in accordance with the approved labeling, is permitted only under certain circumstances. Illegal extralabel use such as use of greater than approved dosages can results in potentially harmful residue in food products.

As an example, in December 2007 the FDA Seattle District Office issued a Warning Letter to the owner of an Oregon dairy after inspection confirmed that the dairy offered a cow for sale for slaughter as food that contained potentially harmful drug residues. The Food Safety and Inspection Service found sulfadimethoxine in the liver at 7.27 parts per million (ppm) and the muscle at 1.60 ppm, and penicillin in the kidney at 2.22 ppm. Tolerances of 0.1 ppm have been established for residues of sulfadimethoxine and 0.05 ppm for residues of penicillin in the uncooked edible tissues of cattle. The investigation also found that the firm held animals under conditions that were so inadequate, e.g., controls were lacking, that medicated animals bearing potentially harmful drug residues due to illegal extralabel use were likely to enter the food supply.

INTERNATIONAL COORDINATION RELATED TO ANIMAL DRUG RESIDUES

The Office of New Animal Drug Evaluation supported the U.S. Trade Representative at the World Trade Organization Appellate Body Hearing in the European Community-Hormones dispute in Geneva in July 2008 through expert consultation provided by Dr. Adele Turzillo. The hearing’s purpose was to consider the European Community’s appeal of the World Trade Organization panel decision affirming the safety of the use of FDA-approved hormones in beef. The appellate decision sustained the U.S. science-based determination of the safety of beef produced using approved production animal drugs, although a procedural appeal by the European Community was under consideration at the end of the year.

Ensuring Feed Safety

THE CHALLENGE

Threats to the safety of the nation’s animal feed supply could come from several sources. Contaminants and unsafe additives in animal feed can harm the animals, as well as humans who consume animal products, and can adversely affect the nation’s food and feed supplies. Improper manufacture of animal feeds can also result in health problems for animals and humans. Animal feed ingredients and mixed feeds including pet food produced and used in this country have a good safety record. However, because oversight of this industry is limited and focused on a few known safety issues, human and animal health problems may be hidden.

CVM is challenged to address these issues through implementation of the FDA’s 2007 Food Protection Plan, the applicable provisions of the 2007 Food and Drug Administration Amendments Act (FDAAA), and other authorities the Center has available to it.

FY 2008 ACCOMPLISHMENTS

Following are highlights of our FY 2008 accomplishments with regard to feed safety. In addition to the actions described below, we completed a variety of ongoing assignments, including approving 49 medicated feed mill licensing applications and supplements; firms that manufacture certain medicated feeds are required to be licensed. We also processed 21 food additive petitions and 61 investigational food additive petitions.

RISK-BASED SYSTEM – ANIMAL FEED SAFETY SYSTEM (AFSS)

Led by a team consisting of members within and outside CVM, our initiative continued during the year to develop a nationwide, comprehensive, risk-based system that is intended to prevent contamination of animal feed and other hazards. The CVM-led AFSS Team has been analyzing the Agency’s feed safety program, identifying areas or “gaps” in which the system could be strengthened, and suggesting approaches to address those gaps.

We are designing the AFSS to detect hazards before feed products are distributed, thus minimizing detrimental animal and human health effects. The AFSS initiative covers the entire continuum of Agency activities from pre-approval of additives for use in feed to establishing limits on feed contaminants; from providing education and training to conducting inspections and taking enforcement actions for ensuring compliance with Agency regulations. The AFSS initiative includes oversight of labeling, production, distribution, and administration of all feed ingredients and mixed feeds at all stages of manufacture, distribution, and use, whether at commercial or non-commercial establishments. Feeds intended for food-producing and other types of animals, such as pets, are included in the AFSS.

With its focus on risk identification and risk-based resource allocation, the AFSS has become an integral part of the Agency’s Food Protection Plan. The AFSS will also be the tracking vehicle for CVM’s implementation of applicable provisions of the FDAAA.

Additional background is available on the AFSS Web page, http://www.fda.gov/AnimalVeterinary/SafetyHealth/AnimalFeedSafetySystemAFSS/default.htm. We describe some of the AFSS accomplishments during the year in the following paragraphs.

Public Meeting on Risk Exposure

The AFSS Team hosted its fifth Public Meeting in May 2008. During the meeting, which provided opportunity for public comment, the team presented changes to the AFSS project in the form of a third draft of the AFSS Framework document (discussed below). The presentation included discussion of newly identified gaps. It also continued the discussion of the risk-ranking model that had been the subject of two previous public meetings. We provided an explanation as to how health consequence scoring is combined with exposure scoring to rank the risk of contaminants in animal feed, using swine feed as an example. We also presented the risk-based method being used to establish priorities in the feed inspectional programs.

Revision to Draft Framework Document

The third draft of the Framework Document, completed in April 2008, adds a new component that covers reporting of unsafe feed. It also identifies gaps in the existing feed safety system related to the reporting of unsafe feed. This third version is posted on CVM’s Web site at http://www.fda.gov/AnimalVeterinary/SafetyHealth/AnimalFeedSafetySystemAFSS/ucm053742.htm.

The changes to the Framework Document came about in part because of the requirements placed on FDA by provisions of the FDAAA. These statutory requirements apply mainly to pet foods, and discussed in detail in the section “Protecting the Health of Companion Animals.” Although pet foods are included in the AFSS, in this section we address primarily those provisions that apply to animal feed other than pet food.

The new component (Component D) is titled “Reporting of Unsafe Feed.” The FDA’s Food Protection Plan identifies the need for the Agency to be more responsive to unsafe food and feed incidents. The Agency needs to know of such incidents before they cause widespread injury or death, and the public needs to be advised about those incidents so they and their pet animals can be protected. The new component identifies two gaps in the effort to meet the requirements of the Food Protection Plan and the FDAAA.

The first gap addresses the need to have a readily accessible registry of incidents that are reportable. The FDAAA directs the FDA to establish a “Reportable Food Registry” to which food and feed incidents would be added by the Agency via an electronic portal. The requirement applies to all animal feeds, including pet foods. CVM is assisting the Center for Food Safety and Applied Nutrition in building the reportable food registry, with CVM having responsibility for the animal feed portion.

The second gap has to do with the fact that reporting of adulterated feed incidents to FDA is currently required only in certain limited circumstances. For example, only FDA-licensed feed mills are required to submit adverse experience reports, and then only for certain medicated feeds. CVM is considering whether to revise its regulations to expand reporting requirements for medicated animal feed incidents.

Regulations to Address Process Control

Process control is a systematic approach designed to ensure feed safety though the identification and use of appropriate controls during the steps of manufacturing, packaging, storage, and distribution of feed ingredients and mixed feed. FDA’s current animal feed safety program does not fully address all aspects of feed safety associated with those steps of all feed ingredients and mixed feed. The FDAAA requires the Agency to adopt processing standards for pet foods; we are expanding our response to include all animal feed.

The AFSS Team during the year continued drafting proposed process control regulations. The process control regulations will seek to prevent, eliminate, or reduce to acceptable levels the potential risks posed to human and animal health, and will be developed through a systems approach in which adequate control steps are established throughout the feed ingredient and mixed feed manufacturing continuum. Closing the identified gaps will result in a safe animal feed supply and thereby improve the safety of human food of animal origin.

AFSS Education and Outreach

Education and outreach are integral and continuing parts of the AFSS. The AFSS Team is identifying which parts of AFSS will affect which stakeholders, and is planning outreach and training programs tailored to those stakeholders. During the year, the AFSS Team gave a presentation at the Association of American Feed Control Officials to update Association members on the status of the initiative. The Team gave additional presentations to several scientific and professional organizations.

THIRD-PARTY CERTIFICATION

FDA’s Food Protection Plan emphasizes the use of certification programs, i.e., programs in which independent third parties certify products as meeting safety (as well as quality) standards. FDA is considering the possibility of establishing third-party certification programs for regulated products. In April 2008, the Agency issued a request for comments on the use of third-party certification programs for food and feed production. In July 2008, the Agency issued a draft guidance, “Voluntary Third-Party Certification Programs for Foods and Feeds,” to generate public comments on a possible program.25

The draft guidance describes the attributes FDA believes a third-party certifier needs in order to be acceptable.

MEDICATED FEED MILL INSPECTIONS – VOLUNTARY SELF-INSPECTION PROGRAM

FDA and the States conducted a total of 453 medicated feed mill inspections during FY 2008. We met the performance goal for FDA inspections (90 inspections) and exceeded the goal for pre-approval inspections by conducting 15 such inspections.

The inspections were conducted according to a risk-based inspection plan we initiated in FY 2008. We provided the FDA District Offices with a prioritized list of medicated feed manufacturing facilities to inspect. We based the list on semi-quantitative risk and facility factors such as compliance status, inspectional history, time since last inspection, and expert opinion.

FDA had during FY 2007 announced plans to implement a voluntary self-inspection program (VSIP) for medicated feed manufacturing, designed to serve as a tool to be used by the FDA District Offices to assist them in prioritizing inspections of medicated feed producing establishments. We placed VSIP on temporary hold before its initiation, however, pending review of the results of the risk-based inspection program initiated during FY 2008. We intend to review data for two fiscal years before deciding how to proceed.

FEED RELATED POISONINGS

A survey of veterinary diagnostic laboratories conducted by Iowa State University under contract with CVM identified the toxicants most frequently implicated in feed contamination poisoning incidents during the past 5 years. The top 10 toxicants in decreasing order of prevalence were: copper, cantharidin, deoxynivalenol, ionophores, fumonisins, ammonia/NPN, nitrate, organophosphates, aflatoxins, and ergot. CVM will use these data, which come from 14 States, as it applies its resources within the scope of risk-based inspections.

DOMESTIC SURVEY AND NATIONAL/INTERNATIONAL COORDINATION RELATED TO DISTILLERS GRAINS

In 2008, we issued a Nationwide Survey of Distillers Grains for Antibiotic Residues, for sample collection by the FDA field offices. As described below, the Office of Research utilized samples collected from this survey for the development of a multi-analyte method for the detection of antibiotic residues in distiller’s grains from fuel ethanol facilities.

Distillers grain is a major byproduct of ethanol distillation. It is rich in nutrients and, as such, is an excellent feed supplement for livestock. With the expansion of ethanol production, increasing amounts of distillers grains are available for feed use. However, there is growing concern over the possibility of antibiotic residues in distillers grains, which may result from the use of antibiotics to prevent bacterial growth during ethanol fermentation. Any residual antibiotics in distillers grains could transfer to animals and pose a potential health risk to the animals as well as to humans that consume food derived from the animals.

In 2008, CVM worked with the Environmental Protection Agency to clarify the respective roles of the agencies with regard to regulatory jurisdiction over the use of antibiotics during fuel ethanol production. FDA regulates distiller byproducts from both potable and fuel ethanol production when the byproducts are used as animal feed and/or feed ingredients, regulating antibiotic residues as food additives. If the distiller byproduct is burned as fuel or disposed of in another non-food/non-feed manner, however, the antibiotics would be considered pesticides and regulated by the Environmental Protection Agency under the Federal Insecticide, Fungicide, and Rodenticide Act.

CVM also worked actively during the year with the U.S. Department of Agriculture’s Food and Agricultural Service and the Canadian Food Inspection Agency to address potential distillers grain trade issues between the United States and Canada as a result of the issuance of the Canadian Food Inspection Agency’s Regulatory Guidance Document on Ethanol Distillers Grains for Livestock Feed in July 2008. The goal is to harmonize policies in this area.

CVM has taken an active role on this issue by participating in several biofuel taskforces, i.e., the Association of American Feed Control Officials biofuel taskforce, the National Grain and Feed Association distillers grain taskforce, and the Department of Energy’s Interagency BioFuel Working Group. These groups are addressing safety concerns and suitability associated with the distillers grain coming from the biofuel industry.

CODEX WORK ON ANIMAL FEED

Members of the Codex Alimentarius Commission, a voluntary international organization that sets food safety standards, agreed at their June 2008 meeting that the Codex should plan to do additional work to further ensure the safety of feed and feed ingredients. From 2000 to 2005, CVM participated as the U.S. Delegate to the Codex ad hoc Intergovernmental Task Force on Animal Feeding, which reached consensus on a Code of Practice on Good Animal Feeding. Codex in June 2008 established an electronic working group, which is currently considering the scope of future Codex work concerning feed standards. Dr. Dan McChesney, Director of CVM’s Office of Surveillance and Compliance, is the U.S. representative to the working group and is coordinating input from U.S. stakeholders on the issues raised in the working group.

RESEARCH RELATED TO FEED CONTAMINANTS

Antibiotics in Byproduct from Ethanol Production

Researchers at CVM continue to work to address critical needs for methods to detect microbiological and chemical contaminants in food and feed. A large focus of the active research has been to develop methods for testing contaminants in distillers grain.

In the past year, our Office of Research scientists developed a method to detect 13 antibiotics in distillers grains. The researchers validated the method for use in distillers dried grain, distillers wet grain, and in corn syrup residue from ethanol production. The method was used during the year to test samples collected as part of the nationwide survey for antibiotic residues in distiller’s grains. At the end of the year, work was in progress to pass the method to FDA field laboratories for use in support of potential regulatory action based on samples to be collected during FY 2009.

Multiple Drug and Contaminant Testing in Feed Samples

CVM scientists continue to focus on the development of methods capable of detecting multiple drugs or contaminants in a single assay of feed. Providing improved methods will allow regulatory laboratories to institute more effective residue testing programs. Researchers during the year completed the development of procedures to include selected pesticides in the multiclass multiresidue method for drugs and other contaminants in animal feeds. We also initiated development of a separate procedure to detect mycotoxins in feeds. Improved methods are needed to detect these naturally occurring toxins in both finished animal feeds and distiller’s grains. These methods will be available for other Federal agencies as well as State regulatory agencies.

Protecting Against Bioterrorism

THE CHALLENGE

There is widespread concern that microbial and other toxic agents could be used in the food chain as weapons to harm human and animal health. FDA is responsible for implementing provisions of the Bioterrorism Act relating to protection of the nation’s food and drug supplies. CVM is working with other Federal agencies to help the nation prepare for a biological emergency, natural disaster, or terrorist attack by making sure that the animal feed supply is safe and that an adequate supply of veterinary drugs would be available in case of emergency.

FY 2008 ACCOMPLISHMENTS

In FY 2008 CVM conducted a number of activities that support FDA’s strategic goal to improve product quality, safety, and availability through better manufacturing and production oversight by protecting the public from microbial or toxic chemical attack and other terrorist threats. We present highlights in the following paragraphs.

PROTECTION AGAINST UNSAFE IMPORTED FEED INGREDIENTS

Soft targets need to be hardened and security gaps need to be filled; these are major priorities for our nation as long as the risk for a terrorist attack remains. Mitigation strategies to reduce the threats and prevent attacks on food and agriculture are essential.

Imported animal feeds and feed ingredients provide an example. Much of the animal feed industry in the United States is dependent upon feed ingredients imported from other countries, and complete feeds are imported from some countries.

As a result of the imported pet food ingredient contamination incident of 2007, CVM worked with the Center for Food Safety and Applied Nutrition’s Prior Notice Center during FY 2008 to develop risked based criteria for targeting inspections of imported animal feeds. “Prior notice” is advance notification to FDA that an article of food, including animal feed, is being offered for import into the United States; this practice was instituted as a result of the Bioterrorism Act of 2002. The Prior Notice Center is now applying the criteria developed by CVM and Center for Food Safety and Applied Nutrition to FDA’s High Risk Prior Notice Targeting Strategies.

EMERGENCY RESPONSE COORDINATORS

During the year, CVM’s Division of Compliance added two emergency response coordinators to its staff, and provided them with initial training related to bioterrorism. They are responsible for responding and coordinating during emergencies, regardless of whether the emergencies are related to bioterrorism.

INTERAGENCY COORDINATION

An important part of CVM’s bioterrorism activities involve coordination with other government agencies. For example, during the year CVM:

  • Shared information with the Steering Committee for the National Veterinary Stockpile to leverage capabilities in the event of a major animal disease outbreak that threatens animal and public health, including delivery mechanisms and circumstances under which the Department of Health and Human Services resources could be tapped. The National Veterinary Stockpile, established by a Homeland Security Presidential Directive, is the national repository of critical veterinary supplies (including vaccines, antiviral, and therapeutic products), equipment, and services necessary to respond to the most damaging animal disease affecting human health and the economy. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service administers the stockpile.
  • Participated in monthly meetings on the safety of imported agricultural products with the U.S. Department of Agriculture’s Food Safety and Inspection Service and the Animal and Plant Health Inspection Service. The meetings include discussion of methods to close gaps in the import system that may affect counterterrorism efforts within agriculture.
  • Participated in the Joint Food and Agriculture Sector quarterly meetings, which were mandated by a Homeland Security Presidential Directive. This group is responsible for collaborating with private sector security partners and encouraging the development of appropriate bioterrorism-related information-sharing and analysis mechanisms within the sector.
  • Participated in the monthly Agricultural Intelligence Group meetings to exchange information and ideas about food security, and to discuss ways in which the participating agencies can best utilize their combined skills, technology, and resources to prevent and respond to agroterrorism threats. The Agricultural Intelligence Group consists of representatives of a number of Federal agencies that meet to discuss and share information on agriculture-related threats and background data in a secure manner.

RESEARCH RELATED TO BIOTERRORISM

The recent attention to biosecurity in animal agriculture has renewed interest in development and evaluation of rapid microbiological screening methods for use in animal feeds and feed commodities. One CVM goal in this area is to develop methods to culture feeds and feed commodities for the presence of bacterial pathogens of veterinary and public health significance. Accomplishing this goal meets the Department objective of improving quality, safety, and availability of food products through better manufacturing and product oversight. In addition to biosecurity, this work also contributes to the Center’s work on antimicrobial resistance and supports development of the AFSS.

CVM’s approach to this challenge has two aspects, as described below.

Establishing a Baseline for Bacillus and Clostridium Contamination of Animal Feed

Using survey samples collected by the FDA field offices, Office of Research scientists are conducting survey programs to determine background levels of the animal pathogen Bacillus anthracis (anthrax) that can routinely be recovered from animal feeds. These data will provide a baseline for comparison against pathogen levels in feed where intentional contamination has occurred. Following the development of isolation methods in 2007, the Office of Research during FY 2008 completed screening of more than 80 feeds and feed commodities for the presence of bacteria from the Bacillus cereus group, which includes B. anthracis. Although we found Bacillus cereus organisms in 25 percent of the samples, none of the strains had features characteristic of B. anthracis. The protocol has been modified to improve the recovery rate of Bacillus species in order to confirm the results obtained to date.

This work is part of our continued efforts to investigate issues of importance to animal feed security, and to support development of AFSS. Upon completion of the Bacillus baseline, screening methods for Clostridium will be developed and used to establish baseline information for this genus.

Sampling of Microbial Species for Prevalence and Antibiotic Susceptibility Profiles

We are establishing culture methods to determine the presence and antibiotic susceptibility of various organisms of interest. Ultimately, this project will evaluate rapid screening methods for their applicability to feed and feed commodities in the United States. This program will result in a better assessment of the role animal feed plays in the introduction of pathogens into the animal production environment and will assess the potential for feed to disseminate resistance determinants in the animal population.

The immediate objective is to develop and implement a national swine feed survey. During FY 2007, CVM Office of Research scientists worked with the CVM Division of Animal Feeds and the FDA Office of Regulatory Affairs to sample complete swine feeds for Salmonella, Escherichia coli, and Enterococcus prevalence and to determine antimicrobial susceptibility profiles of recovered isolates. The Office of Regulatory Affairs accomplished the Salmonella testing. CVM scientists cultured sub-samples of feed and feed components for Enterococcus and E. coli. In FY 2007 and FY 2008, we found Enterococcus in 209 of 290 feed samples and E. coli in 46 of 277 samples. Antimicrobial susceptibility testing is ongoing, continuing into FY 2009. The data we are gathering will be used to guide the development of rapid screening methods for animal feeds.

Ensuring the Safety of Animal Clones and Genetically Engineered Animals

THE CHALLENGE

The application of cloning and genetic engineering to the production of animals, and products derived from animals, continues to grow. Animal cloning, an assisted reproductive technology, is seen as a means of expanding populations of cattle, swine, and goats with desired characteristics. Genetic engineering involves the use of recombinant DNA technology26 to add or alter traits in animals. Genetic engineers are investigating a wide range of applications to produce genetically engineered animals. Producing animals through cloning and genetic engineering raises potential food and animal safety issues, and CVM needs to provide appropriate regulatory oversight based on a thorough understanding of the scientific and risk issues that are involved.

FY 2008 ACCOMPLISHMENTS

We focused much of our effort during the year on the development and publication of draft guidance on the regulation of genetically engineered animals. The guidance is intended to clarify FDA’s regulation of genetically engineered animals. It provides recommendations to producers and developers of genetically engineered animals regarding the kinds of data and information that could help them meet their obligations and responsibilities under the law, including requirements for approvals. Also during the year, we issued a final risk assessment on the regulation of cloning.

REGULATION OF GENETICALLY ENGINEERED ANIMALS

CVM has been advising developers and producers of genetically engineered animals as to regulatory requirements since the technology became of commercial interest in the early 1990s. We have based our advice on the premise that these animals are to be regulated under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act.

With genetically engineered animals approaching commercialization, the Center – working closely with the Office of the Commissioner – during FY 2008 prepared a draft guidance for public comment. (The draft was finalized in FY 2009.) The purpose of the guidance is to clarify for the industry, the public, and other stakeholders the statutory and regulatory authorities for regulating these animals. It also provides recommendations to the industry members on how they can meet their responsibilities and obligations under the new animal drug provisions of the Federal Food, Drug, and Cosmetic Act.

The Agency released the draft guidance for public comment in September 2008. The guidance is titled “GFI #187 – Containing Heritable rDNA Constructs (Draft).”

Genetic engineering generally refers to the use of recombinant DNA techniques to introduce new characteristics or traits into an animal, plant, or other organism. Many kinds of genetically engineered animals are in development, for a variety of purposes including production of pharmaceuticals that are difficult to produce in sufficient quantities by other means; production of scarce cells, tissues or organs for transplantation; and food purposes. Examples of the latter are animals that are resistant to disease (such as mastitis) or have improved nutritional or growth characteristics.

CVM will regulate all genetically engineered animals regardless of their intended use. The appropriate FDA Centers will have regulatory authority over substances produced by genetically engineered animal that are to be used in, or as, human drugs, biologics, or devices. The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service will have responsibility for approving veterinary biologics produced through the use of genetically engineered animals.

Issuance of the guidance is particularly timely for several reasons. First, based on our interactions with genetically engineered animal developers over a period of years, we believe that we have a good idea of the kind of guidance that would be most helpful to industry. We also believe that publishing the guidance gives the public a better understanding of FDA’s role in this important developing area. Finally, with the recent adoption of the Codex Alimentarius Commission’s “Guideline for Assessing the Food Safety of Food from rDNA Animals” (June 2008; ftp://ftp.fao.org/codex/Alinorm08/al3103Ae.pdf) – which provides internationally recognized recommendations for assessing the safety of food from genetically engineered animals – we believe that it is important that developers around the world fully understand the rigorous regulatory requirements that these animals, and the food products derived from them, will have to meet in the United States. (FDA’s draft guidance is consistent with that provided in the Codex guideline.)

CVM’s regulation of genetically engineered animals and their products for food use will be consistent with how the Center regulates conventional new animal drugs, but will include features unique to genetically engineered animals. A major purpose of the draft guidance is to explain how those regulations apply to genetically engineered animals. For example, the guidance recommends a review process that includes seven categories: product definition; molecular characterization of the construct (i.e., a description of the rDNA construct27) and how it is assembled; molecular characterization of the genetically engineered animal lineage; phenotypic characterization of the genetically engineered animal (comprehensive data on the characteristics of the genetically engineered animal and its health); durability plan (the sponsor’s plan to demonstrate that the modification will remain the same over time, and continue to have the same effect); environmental and food/feed safety assessments; and claim validation (a demonstration that the genetically engineered animal does fulfill the product definition stated in the beginning of the review process).

Any animal containing an rDNA construct that is intended to alter the animal’s structure or function is subject to pre-market approval by FDA prior to commercialization. However, based on level of risk, CVM may not require approval of certain categories of genetically engineered animals, such laboratory animals used for research. The Center may also exercise enforcement discretion with respect to the marketing of unapproved genetically engineered animals, as it has already done for an aquarium fish genetically engineered to glow in the dark. However, the Center expects to require approval of all genetically engineered animals intended to go into the human food supply.

CLONING RISK ASSESSMENT

In January 2008, CVM completed a 6-year process of performing an assessment of the risks that somatic cell nuclear transfer (cloning) pose to the health of animals involved in the cloning process, as well as the food consumption risks of edible products from clones and their progeny. The Center did so by issuing a final risk assessment, following review of comments on a draft risk assessment made available for public comment in December 2006. The document is “GFI #179 – Guidance for Industry Use of Animal Clones and Clone Progeny for Human Food and Animal Feeds (Final).”

The guideline development process involved working closely with industry stakeholders who voluntarily generated data on animal health and food composition, consideration by the Veterinary Medicine Advisory Committee, and review of more than 30,500 comments submitted in response to the draft risk assessment. We have posted a summary of the comments and our responses to them on the CVM Web site.

The final draft does not incorporate significant changes from the draft risk assessment, which is evidence of the thorough consideration of the scientific data that supported the draft risk assessment. The risk assessment concludes that food products from healthy cattle, swine, and goat clones and their progeny are as safe as food produced by conventionally bred animals. The accompanying risk management plan and guidance for industry provide recommendations to producers and breeders of clones on how to handle clones and their progeny.

With the completion of the final draft, we turned our attention to working with other U.S. government agencies, and international agencies, to help ensure a smooth and orderly transition of food products from the cloning process into domestic and international markets. CVM’s ongoing interactions with the trade components of the U.S. government help to ensure that factual information is communicated about animal health and food safety, and that the U.S. government’s position is substantiated in the event of any World Trade Organization disputes. Dr. Larisa Rudenko, CVM’s Senior Advisor for Biotechnology, serves as a representative to U.S. Department of Agriculture’s Foreign Agricultural Service and assists the U.S. Trade Representative as a technical expert in discussions with counterparts of U.S. trading partners.

The United States has taken the lead internationally in the adoption of science-based decisions regarding the safety of food from clones. During FY 2008, Dr. Rudenko served on the European Food Safety Authority’s28 working group on animal cloning, the first time an American had been asked to do so. She helped that group develop its scientific position on clones; European Food Safety Authority’s food safety conclusions on clones and their progeny are consistent with FDA’s decision on the safety of food from clones and their progeny.

Additional Surveillance and Compliance Actions to Protect Public and Animal Health

THE CHALLENGE

Surveillance and compliance activities are key parts of our efforts with regard to antimicrobial resistance, BSE, drug residues, feed safety, and other crosscutting issues described above. We have had challenges in additional areas that are related to our core functions of compliance-related actions and post-approval monitoring. These challenges include acting against specific threats to public and animal health, monitoring to assess post-approval drug safety, taking steps to ensure proper manufacture of approved drugs, regulating animal drug compounding, controlling the marketing of unapproved drugs, and responding to other challenges.

FY 2008 ACCOMPLISHMENTS

Following are highlights of our accomplishments during the past fiscal year.

COMPLIANCE ACTIONS

Risk-Based Inspection Planning

As explained in the section on “Ensuring Food Safety,” during the year as part of the inspection planning process the Center initiated the use of risk-based assessment methods for identifying regulated firms of highest risk. Besides medicated feed inspections, we used this approach for inspections involving drug manufacturing, enforcing the BSE rule, and following up on tissue residue violations and feed contamination incidents. This approach means that the Agency will be utilizing its resources in the inspection of firms associated with the greatest risk of adversely affecting public and animal health.

Compliance Action Processing

During the year, we processed the following actions: injunctions (5), contempts of injunction (2), product seizure (1), and Warning Letters (48). We also processed a total of 247 recalls, broken down as follows:

  • Class I (8 firms, 18 products)
  • Class II (13 firms, 107 products)
  • Class III (13 firms, 122 products)29

Regulation of Extralabel Use

Pandemic Influenza Preparedness – extralabel use of adamantanes and neuraminidase inhibitors. CVM researchers during the year made progress in the development of a method capable of detecting illegal use of antiviral drugs, approved for human use, in certain poultry species. The method will be used in enforcing a March 2006 FDA rule prohibiting the extralabel use of adamantanes and neuraminidase inhibitors in chickens, turkeys, and ducks. This rule responded to a November 2005 statement from the World Health Organization, the United Nation’s Food and Agriculture Organization, and the World Organization for Animal Health, urging their Member States not to use antivirals in animals in order to preserve their efficacy for human use in the case of an influenza pandemic.

In collaboration with the Central Science Laboratory (York, UK), researchers at CVM have developed a method capable of detecting four antiviral compounds and a known metabolite of one compound in chicken tissues. The compounds are amantadine, rimantadine, oseltamivir phosphate (TAMIFLU), and zanamivir (RELENZA), and the metabolite is oseltamivir carboxylate, an active metabolite of TAMIFLU. Metabolism studies are currently being conducted to verify the choice of the marker compounds in hens. Preliminary results from the 14C-rimantadine metabolism study show several metabolites and suggest that parent rimantadine may not be an appropriate marker residue. Work is underway to identify the metabolites, establish a marker residue, and modify the method. We are also working to expand the method for use in turkeys and ducks and to validate the method.

Cephalosporin use in food-producing animals. In July 2008, CVM issued an order prohibiting the extralabel use of the cephalosporin class of antimicrobial drugs in food-producing animals including, but not limited to, cattle, swine, chickens, and turkeys. The purpose was to protect consumers against antimicrobial-resistant strains of zoonotic30 foodborne bacterial pathogens. FDA had gathered evidence showing that the extralabel use of cephalosporins in food-producing animals is likely to contribute to the emergence of resistance and compromise human therapies. The law provides for a delayed effective date for the order, to permit time for public comment and review of those comments by FDA. In response to the July order, we received a significant number of substantive comments. Given the substance of the comments, we did not believe a thorough review could be completed before the order of prohibition was due to take effect. So, on November 25, 2008, we revoked the order to give us sufficient time to consider the comments fully.

Once our comment analysis is completed, we may reissue a modified prohibition order. Any new order would be issued following the procedures established by regulation; that is, a new order would include a 60-day public comment period.

Compounding

In July 2008, the U.S. Circuit Court of Appeals for the Fifth Circuit upheld FDA’s authority to regulate compounded drugs for animal use under the new animal drug provision of the Federal Food, Drug and Cosmetic Act.31 The court held that, unless the compounded drugs are exempt under provision of the Animal Medicinal Drug Use Clarification Act, they are subject to pre-approval and other requirements of the Federal Food, Drug, and Cosmetic Act.

Generally, FDA will defer to State authorities regarding the day-to-day regulation of compounding by veterinarians and pharmacists of animal and human drugs that are intended for use in animals. However, when the scope and nature of activities of veterinarians and pharmacists are similar to those of drug manufacturers and result in significant violations of the new animal drug, adulteration, or misbranding provisions of the Federal Food, Drug, and Cosmetic Act, FDA has determined that it will seriously consider enforcement action. In determining whether to initiate such an action, the Agency will consider a number of factors that are set forth in Compliance Policy Guide 608.400.

Conviction of Florida Reptile Firm for Selling Small Turtles

In July 2008, a Hollywood, FL, reptile firm was convicted and sentenced for violating a public health law banning the sale of turtles with shells less than 4 in. long. A ban on the sale of such turtles has been in effect since 1975 due to the public health impact of turtle-associated salmonellosis. FDA enforces the regulation under authority provided in the Public Health Service Act and in cooperation with State and local health jurisdictions. FDA’s Miami District Office of Criminal Investigations, U.S. Fish and Wildlife Service, and CVM cooperated in the investigation.

Removal of Restrictions on African Rodents, Prairie Dogs, and Other Animals

FDA in September 2008 removed its restrictions on the interstate movement of certain African rodents and prairie dogs that can carry or spread monkey pox. The Agency determined that such measures are no longer needed because there have been no new cases of monkey pox in the United States since an outbreak in 2003; a risk assessment published in 2006 suggested that the risk of further domestically acquired human monkey pox cases in the United States is low; and the Centers for Disease Control and Prevention rule that prohibits the importation of all African rodents remains in effect. FDA and the Centers for Disease Control and Prevention jointly implemented restrictions in 2003 in response to a domestic outbreak of human monkey pox, a rare viral disease that can be fatal in humans and is found mostly in central and western Africa.

SURVEILLANCE ACTIONS

In FY 2008, the Division of Surveillance received more than 3,400 Drug Experience Reports containing promotional pieces, clinical data, and Adverse Drug Experience information for our review. Following the review of these promotional pieces, the Post Approval Review Team issued two Warning Letters and one Untitled Letter requesting discontinuation of violative labeling and advertising materials. The letters addressed issues of misleading human safety information, minimization of risk to humans potentially exposed to the drug, unsubstantiated claims of effectiveness regarding zoonotic disease in humans, and unsubstantiated safety and superiority claims.

The Division completed a number of Medically Necessary Veterinary Product determinations and Health Hazard Evaluations as requested over the past year.

Throughout 2008, the Division worked with sponsors to implement product label changes that are intended to improve the safety of the products.

Several months after the September 2007 approval of COMFORTIS (spinosad) for prevention and treatment of flea infestations on dogs, the safety review team reported a significant increase in adverse drug reports for COMFORTIS that were associated with the concurrent extralabel, high dose use of ivermectin. The Division of Surveillance worked with the sponsor to investigate this safety issue and to disseminate informational material for veterinarians, including a CVM Update. We issued another Update in response to reports of precipitate forming in opened or leaky bottles of EQVALAN (ivermectin) Liquid for Horses. In this case, the Division also worked with the sponsor to recondition the product and send out technical bulletins.

Enhancing Productivity through Achievement of Leadership and Management Objectives

THE CHALLENGE

The challenge for the Office of Management was to provide the essential executive leadership and knowledgeable support necessary for CVM to meet the 2008 Departmental objectives for executive leadership and management, and certain CVM-specific program objectives. The organization’s challenge also includes continued implementation and guidance of the improved management systems and business practices, as outlined by the Department of Health and Human Services and FDA.

FY 2008 ACCOMPLISHMENTS

Through the leadership and active guidance of Office of Management, the Center successfully met specific objectives for FY 2008, as described in the following significant outcomes and achievements.

EXECUTIVE LEADERSHIP AND MANAGEMENT RESULTS OBJECTIVES

As summarized above in the section “Accomplishing Department and Agency Objectives,” CVM successful met the FY 2008 Departmental executive leadership and management objectives as applied to CVM’s sphere of activity. Here are just a few examples to illustrate:

Executive Leadership Results Objective: Improve the Recruitment Process to Fully Support the Agency Hiring Surge Goals.

The Office of Management developed and implemented a CVM strategic recruitment process in FY 2008 that now serves as a “best practice” Agency-wide. This new front-end recruitment strategy is an endeavor that engages the supervisor early in the recruitment process to discuss required competencies and experience, desirable qualification, “Quick Hire” questions, hiring flexibilities, potential hiring hurdles, and selective factors. The new process has strengthened our hiring procedures and significantly clarified the Federal hiring practices for prospective CVM job candidates and supervisors. Due to the high efficiency of the new process, CVM was the first Center to meet and exceed its Surge I hiring goals, as required under the FDA Hiring Surge initiative.

Executive Leadership Results Objective: Contribute to the Leadership of Agency-Driven Priorities and Objectives.

Office of Management staff provided vital information, data, and guidance for major Agency-wide initiatives in FY 2008, with results that included the following:

FDA Salary Survey – Working with a consulting firm, the Office of Management completed the annual Agency salary survey. The results are used Agency-wide by the FDA Executive Resources Board for pay requests that require comparative salary documentation, such as requests for retention incentives above the minimum rates and recruitment incentives. The salary survey provides a uniform comparison of salaries that can be used throughout the Agency for a more rapid and equitable resolution of salary issues.

“Any 80” Integrated Time and Attendance System (ITAS) Policy – The Office of Management worked with the Agency to establish and interpret policy to resolve “Any 80” ITAS issues. (“Any 80” refers to alternative and flexible work schedules under which employees meet the requirement of working 80 hours during each 2-week pay period.) This effort helped the Agency to minimize disruption due to the 2008 implementation of the new timekeeping system required throughout the Agency to implement the work schedule policy.

Retention Allowance Form – Office of Management personnel revised the Agency’s Retention Allowance Form to combine the Office of Personnel Management requirements and FDA guidance. The revised form aligns the process for retention of exemplary employees to Department goals. Its use by managers helps ensure the retention of such employees.

Executive Management Results Objective: Initiate the CVM Succession Plan.

The Office of Management provided the vision and direction for the development of the CVM Succession Plan during 2008. This plan establishes the programs and processes necessary to ensure CVM’s active preparation for its future staffing and succession planning needs. The plan is intended to ensure the Center’s recruiting and hiring the right people, setting clear expectations for the new employees, and developing and motivating both the new and current staff members. The plan emphasizes the Center’s guiding philosophy that “leadership belongs to all employees.” It also emphasizes and encourages all employees to be knowledgeable stewards of the Center’s resources, as well as to understand and advance the high performance goals of CVM. At the core of the Succession Plan is the CVM Competency Model that defines the professional and leadership competencies that are necessary to successfully meet the requirements of Center-specific job roles.

PROGRAM RESULTS OBJECTIVES

Program Results Objective: Guide CVM Efforts through the FDA Bioinformatics Board.

CVM’s Associate Director for Management serves as the lead CVM representative to the Agency’s Bioinformatics Board, which provides business leadership and governance to the management of business automation and IT investments throughout the Agency. It proactively supports and champions enterprise strategies that enable the strategic deployment of IT resources. Through the Office of Management efforts in FY 2008, CVM has evolved a more mature process for managing its IT investments and identifying its IT requirement to the Bioinformatics Board, thereby permitting CVM to better support the mission of the FDA Bioinformatics Board.

Program Results Objective: Provide Effective Administration of Animal Drug User Fee Act.

The Office of Management effectively directed the administrative management of the Animal Drug User Fee Act program, accomplishing 100 percent of the program’s activities within required timeframes, during FY 2008, including all deliverables, fee schedules, and Congressional reports. At the same time, the Office of Management maintained full adherence to budget execution and control responsibilities. The actions ensured the proper management of the additional revenues obtained through Animal Drug User Fee Act to enhance the review program, improve communications, and develop guidance, policy, and procedural documents to meet the challenging performance goals associated with this program.

Program Results Objective: Gain Approval for Animal Drug User Fee Act/Animal Generic Drug User Fee Act Legislation.

Two pieces of vital legislation were passed by Congress and signed by the President in 2008; the Animal Generic Drug User Fee Act and the reauthorization of the Animal Drug User Fee Act (ADUFA II). The Associate Director for Management co-led the effort. These critically important actions ensure sound financial footing, providing sustained revenue for sustainable performance. They make it possible for safe and effective drug products to reach the market more rapidly. ADUFA II has resulted in a 30 percent increase in revenues in the first year of the program.

Program Results Objective: Collaborate with the Agency to Meet FDA/CVM Electronic Document Storage and Review Project Objectives.

CVM collaborated with the Center for Devices and Radiological Health to improve business processes for a more robust electronic document management and submission environment. By migrating in 2008 to an Electronic Document Management system shared with the Center for Devices and Radiological Health, CVM achieved a 10 percent reduction in IT infrastructure costs. More importantly, CVM, the Center for Devices and Radiological Health, and more recently the Center for Biologics Evaluation and Research, have started on the path toward a common Electronic Document Repository. CVM also is leveraging Center for Drugs and Radiological Health’s “eSubmitter” and “eReview” tools as potential solutions for CVM stakeholders to use in electronic submissions and for CVM staff to use in their review of electronic submissions. Through this collaboration, CVM, Center for Devices and Radiological Health, and the Center for Biologics Evaluation and Research have taken a critical step toward more effectively aligning business processes, supporting systems, and technology.

Program Results Objective: Enhance the Virtual CVM Staff College Classroom Environment.

The CVM Staff College increased utilization of the enhanced CVM virtual classroom during FY 2008 by delivering 10 seminars via synchronous live Internet technology. The Staff College provided the expertise for this vital initiative to increase global collaboration and communication between CVM scientists and their national and international colleagues, enriching all participants with the latest frontiers of science and greater knowledge of emerging technologies.

Program Results Objective: Develop CVM Career/Leadership Development Programs.

The CVM Staff College developed and delivered during FY 2008 a CVM Management Course for New Supervisors (95 credit hours), required to be taken within a CVM supervisor’s first year. The College also developed and delivered a three-module (220 credit hours) Leadership Development Program. Both programs have rigorous, college-level curricula and are skillfully structured to strengthen participants’ skills and abilities based upon the Center’s identified leadership and managerial core competencies. These new programs serve as models for the Agency.

Leveraging Productivity through Partnerships

THE CHALLENGE

FDA and CVM continuously seek out partnering opportunities to maximize the use of available resources. Our success in promoting and protecting the public health depends in large part not only on active involvement by our stakeholders, but also partnerships with those whose goals align with ours. We are also challenged to collaborate with governments of other nations and international organizations as we work toward harmonization in regulatory decisions and standards that offer maximum protection of public health and that benefit U.S. interests in international markets.

FY 2008 ACCOMPLISHMENTS

We continued to work under a number of partnering arrangements during the year, collaborating with academic institutions, scientific and professional groups, government at all levels, industry, and others in the domestic arena. These collaborations have strengthened our research and epidemiological efforts.

As a powerful demonstration of CVM’s extensive involvement in leveraging and collaboration arrangements, a number of CVM staff members (along with many more individuals from other parts of FDA, other government agencies, academic institutions, and industry) received leveraging/collaboration awards during the FY 2008 FDA awards ceremonies. One such award recipient was Dr. Dave Erdahl, leader of the U.S. Fish and Wildlife Services Aquatic Animal Drug Approval Partnership Program (USFWS/AADAP), for exceptional leadership, outstanding coordination of resources, and sustained efforts in the development of data for the approval of new animal drugs for aquaculture. AADAP’s mission is “working with our partners to conserve, protect, and enhance the Nation’s fishery resources by coordinating activities to obtain FDA approval for drugs, chemicals, and therapeutants needed in aquaculture and fisheries management programs.” Dr. Erdahl directs a staff that has been involved in the development of data for approvals of new animal drug applications for drugs used in aquaculture. The data generated by AADAP underlie our newest approvals, including the first in-feed antimicrobial approved for furunculosis in freshwater-reared salmonids in 20 years, AQUAFLOR.

We were also active during the year in collaborative efforts with other nations and international groups. We described many of these working arrangements in the sections on major accomplishments above, and we highlight several examples below.

DOMESTIC COLLABORATION

Aquaculture Drugs

The approvals during FY 2008 of two aquaculture drugs provide examples of collaborative efforts that brought tangible, positive results for the aquaculture industry, public fisheries, and the consumer. These cooperative undertakings were unique in that they involved public and private entities, and several Federal as well as State agencies. The approvals, described in more detail in the section on minor uses and minor species, included:

Oxytetracycline for use in salmonids and trout. These approvals are the result of cooperation between the pharmaceutical company sponsor, Phibro Animal Health, and public sector researchers – the USFWS/AADAP and the U.S. Geological Survey’s Upper Midwest Environmental Science Center (USGS/UMESC). USFWS/AADAP and USGS/UMESC provided data to support the approval.

Florfenicol for use in salmonids. The approval of AQUAFLOR resulted from cooperation between the pharmaceutical company sponsor, Schering-Plough Animal Health Corp., and public sector researchers. The following government groups made scientific contributions that supported the approval: the USFWS/AADAP, USGS/UMESC, and the Montana Department of Fish, Wildlife, and Parks.

14th Annual Aquaculture Drug Approval Coordination Workshop. As in past years, CVM staff from several Offices participated during the year in the annual workshop held in July 2008, hosted by the USFWS, the USGS, and the U.S. Department of Agriculture’s Agricultural Research Service. The purpose of the workshop is to foster collaborative efforts between private and public sectors to develop the data needed for the approval of animal drugs for aquatic species. Research conducted as a result of the collaborations established during previous workshops resulted, among other things, in the approvals of the two important disease management drugs described above. As an outgrowth of the workshop, CVM collaborated with USFWS/AADAP on the revision of a poster that is intended to be a reference guide for aquaculture drug approvals as part of CVM’s Animal Health Literacy Campaign. Laminated copies of the poster are available through CVM’s Communications Staff or by contacting AADAP directly at www.fws.gov/fisheries/aadap/Poster_introduction.htm. AADAP will be distributing the posters at various aquaculture scientific meetings throughout the coming year. The poster is suitable for display in the hatchery, laboratory, office, or classroom – wherever fisheries staff members need quick access to aquaculture drug information.

Research

In vivo/in vitro and interspecies comparisons – Critical Path research. This is a joint project between CVM and the Office of Generic Drugs in FDA’s Center for Drug Evaluation and Research, and with the participation of the University of Maryland School of Pharmacy, Department of Pharmaceutics. The Center for Drug Evaluation and Research is determining the impact of the critical manufacturing variables on in vivo bioavailability in humans. University of Maryland is providing preformulation development, analytical testing, and stability studies; conducting the product quality test procedures; and performing human study and analysis of human and canine blood samples. CVM is responsible for formulation design, protocol development, and data analysis (manufacturing variables and in vivo-in vitro correlations [IVIVC]) in dogs.

The goal of the work, initiated during FY 2008, is the development of immediate release oral dosage form drugs for predicting IVIVCs in dogs and humans, and for generating interspecies IVIVC comparisons for class II drugs, i.e., low soluble, highly permeable drugs. In developing the drugs, we will use the concept of quality by design. Quality by design means building quality into the product while it is going through the manufacturing process by carefully evaluating all attributes that characterize quality from the early stage of development and throughout the product lifecycle, rather than waiting for the post production testing phases. By using immediate release products we can ascertain whether the physiological differences between dogs and humans leads to dissimilarity of the critical manufacturing variables.

We are examining the relationship between in vitro drug release and in vivo drug absorption, to determine if the relationship between in vitro drug release and in vivo drug release in dogs is predictable from data generated in humans, and vice versa. Information gained from this study could aid in the evaluation of human and animal drugs. Information gained from the manufacturing component can be used to set specifications so that that product performance can be carefully controlled through online monitoring systems.

Salmonella diversity studies – critical path collaboration studies. CVM scientists collaborated during the year with FDA’s Center for Food Safety and Applied Nutrition to investigate Salmonella diversity using a novel 35 genome Salmonella microarray. This program examines Salmonella enterica serovars of medical importance for antimicrobial resistance genes, virulence genes, mobile genetic elements, single nucleotide polymorphisms, and evolutionary relatedness using a newly developed and highly dense Affymetrix microarray design. Preliminary data from more than 100 Salmonella strains tested over a number of years validated the capacity of the method to discriminate closely related strains and detect genes important to virulence and antimicrobial resistance. These data will help increase the timeliness and specificity of monitoring of FDA regulated food and animal feed products for microbiological contamination.

DNA fingerprinting study. CVM scientists during the year generated more than 1,000 new DNA fingerprinting profiles of Salmonella, Campylobacter, E. coli Bacillus isolated from retail meats, live animals, animal feed, and fresh produce. We shared the data with CDC PulseNet, the national molecular subtyping network for foodborne disease surveillance, to help populate the reference database of foodborne bacteria with strain types from retail meat products. Providing this information to the CDC database helps meet the FDA Strategic Plan and Food Protection Plan objectives of detecting safety problems earlier, and better targeting interventions to prevent harm to consumers.

INTERNATIONAL COLLABORATION

We described CVM’s participation in certain international efforts to establish standards in previous sections, including the section related to animal clones and genetically engineered animals. Following are additional examples of CVM’s activity and influence in international collaborative activities during the fiscal year, especially as related to animal drug approvals. The actions included expanding lines of communication, making arrangements for exchanging scientific and regulatory information, and providing expert advice and consultation. These accomplishments furthered the public health mission of FDA by ensuring that high quality scientific information is generated, and that regulatory decisions/standards are established on a global basis.

Our participation and accomplishments in this area included:

Participation in deliberations of the Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF).

This committee is part of the Codex Alimentarius Commission, an intergovernmental subsidiary of the United Nations Food and Agriculture Organization (FAO) and World Health Organization (WHO). The CCRVDF develops standards, concepts, and principles applying to veterinary drug residue in food; e.g., it recommends Maximum Residue Limits (MRLs) for veterinary drugs. Dr. Steven Vaughn, Director of the Office of New Animal Drug Evaluation and United States Delegate to CCRVDF, led the U.S. Delegation to CCRVDF as it briefed U.S. government representatives to the July 2008 Codex Alimentarius Commission meeting on issues specific to CCVDF. Dr. Vaughn and members of the U.S. Delegation to CCRVDF met with the U.S. Meat Export Federation on issues impacting fair trade, and participated in outreach efforts to other countries on specific issues, including MRLs for ractopamine.

Participation in activities of the Joint FAO/WHO Expert Committee on Food Additives (JECFA).

JECFA is an international expert scientific committee that evaluates food additives, contaminants, naturally occurring toxicants, and residues of veterinary drugs in food. Dr. Kevin Greenlees and Dr. Lynn Friedlander participated during the year in a JECFA evaluation of nine veterinary drugs, which CCRVDF had requested so that it could establish international standards for residues of the drugs. In addition, Dr. Greenlees chaired a working group that developed a concept paper for discussion on a decision tree approach for the JECFA evaluation of veterinary drugs.

Participation in a number of coordination meetings and conferences between regulatory bodies.

This participation included quarterly meetings for exchange of information with our regulatory counterparts in Canada and Europe. For example, a group of six scientists from the Office of New Animal Drug Evaluation’s Division of Human Food Safety met with their counterparts in the Canadian Veterinary Drugs Directorate in August 2008 to discuss the human food safety review process and human food safety criteria for specific veterinary drugs, and to identify areas for harmonization. CVM also facilitated the exchange of information between regulatory bodies by sharing its scientific reviews for specific veterinary drug products with the Canadian Veterinary Drugs Directorate.

Providing expert advice, consultation, and organizational expertise in other contexts.

This activity included:

  • Dr. Devaraya Jagannath, a member of the micronucleus committee of the Organisation for Economic Co-operation and Development, assisted in the development of a protocol for a new in vitro micronucleus assay for use as part of the genetic toxicology evaluation of veterinary drugs. Along with other FDA members, he provided input into the World Health Organization/International Programme on Chemical Safety white paper on the use of genetic toxicology data in a risk assessment approach to evaluating human food safety.
  • Dr. Haydée Fernández organized a meeting of international scientific experts, held at CVM in April 2008, to share experiences gained in the implementation of International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) GL 36, concerning regulation of antimicrobial drug residues in food. The result of the meeting was a recommendation to the VICH Steering Committee that the report, though very useful in its present form, be revised and clarified.
  • Drs. Lynn Friedlander, Haydée Fernández, and Steve Yan organized and presented a workshop entitled “Update on Human Food Safety Requirements for Antimicrobial Veterinary Drugs Approval” in September 2008 in Asuncion, Paraguay. The audience included regulatory officials, industry scientists, and academia from Latin American countries.
  • Dr. Fernández continued to provide technical assistance to regulatory officials of various Latin American countries, including Guatemala, Chile, and Paraguay, in response to questions about the human food safety requirements for approval of new animal drugs.
Communicating with Stakeholders

THE CHALLENGE

To do the best job it can, CVM must communicate with its stakeholders. Animal drug and feed companies, veterinarians, and livestock producers must know about new policies and regulations as soon as possible, particularly because this information helps stakeholders comply with FDA regulations. Consumers and pet owners need to have their questions answered, and know what steps CVM has taken to protect the food supply and keep their pets safe. CVM must present clear information to diverse audiences about programs and initiatives that are sometimes technical, and usually quite complex. When done successfully, proper communication will help ensure correct adherence to the regulations dealing with human and animal health, and that consumers are well informed and capable of understanding the issues.

FY 2008 ACCOMPLISHMENTS

We undertook a broad range of initiatives to provide important information on public health issues, and on CVM programs and accomplishments during the year. Our new Animal Health Literacy Campaign (described under “Some Highlights from Fiscal Year 2008”) has been a major focus. Our Communications Staff provides leadership in many of the Center’s outreach initiatives, but all of our offices also take leadership and play active roles in the Center’s effort to communicate with our constituents. The following highlights illustrate the range of Center-wide participation in communications efforts.

NEW PUBLIC-ACCESS DATABASE OF ANIMAL DRUG APPROVALS

During the year, CVM completed work on a new database of approved animal drugs. Titled “Animal Drugs @ FDA,” the database is a publicly accessible Web-based application available through the CVM home page. “Animal Drugs @ FDA” replaces the “Database of Approved Animal Drug Products,” or “Green Book,” a database that was previously developed and managed by the Virginia-Maryland Regional College of Veterinary Medicine Drug Information Laboratory at Virginia Tech.

The new application allows users to search for detailed descriptions of all FDA-approved new animal drugs. The search tool not only allows users to conduct simple word searches, but is also capable of more complex searches through the following eight specific search criteria: NADA/ANADA number, sponsor, ingredients, proprietary name, dose form, route, species, or indication.

WARNING TO PET OWNERS: SALMONELLA FROM PET TURTLES

Our communication responsibility includes providing timely information on health issues to animal owners. For example, CVM provided scientific information for a January 2008 FDA Consumer article that updated previously published information on the danger of contracting Salmonella from pet turtles. The updated article – which included recent data from the Centers for Disease Control and Prevention – provides information on the rise of turtle-related Salmonella infections, identifies those who are at most risk, and provides advice to consumers. To read the complete article and to access more information about turtle safety, see www.fda.gov/consumer/updates/turtles012508.htm.

EXPANDED EXHIBIT PROGRAM

We expanded our exhibit program during the year, taking our story to 11 conferences and annual meetings of professional, scientific, industry, and producer organizations across the country. We use the exhibits to provide information on animal health issues and CVM’s programs, and will use them to promote the Animal Health Literacy Campaign. Some of the topics we emphasized this year were the Minor Use and Minor Species Animal Health Act, Cloning Risk Assessment, Animal Feed Safety System, Genetically Engineered Animals, the proposed ban on extralabel use of cephalosporins in food animals, the availability of information on non-steroidal anti-inflammatory drugs, and CVM e-mail notification of new items posted on “What’s New” on CVM Home Page.

Appendices

Appendix A: Significant Regulations, Guidances, and Other Documents

DOCUMENT DEVELOPMENT PROCESS

The preparation of regulations, guidances, and other documents intended for the public is a Center-wide responsibility. However, much of the effort is carried out by the Policy and Regulations Staff within the Office of the Director. For example, the Policy and Regulations Staff is primarily responsible for coordinating regulation development for CVM. In doing so, the Policy and Regulations Staff works with CVM subject matter experts and with FDA technical and legal experts in developing the regulations. This responsibility includes ensuring that the rule complies with Federal laws. The Policy and Regulations Staff is also the focal point for development, clearance, and issuance of guidance documents in CVM. It ensures that all guidance documents are issued in accordance with 21 CFR 10.115, the Good Guidance Practices regulation. The staff shepherds the documents through the clearance process, which involves cooperation with subject matter, legal, and paperwork reduction staff.

SIGNIFICANT REGULATIONS, GUIDANCES, AND OTHER DOCUMENTS

Guidances

Guidance for Industry #178 – Recommended Study Design and Evaluation of Effectiveness Studies for Swine Respiratory Disease Claims. October 2, 2007.

Guidance for Industry #179 – Guidance for Industry Use of Animal Clones and Clone Progeny for Human Food and Animal Feeds. January 15, 2008.

Draft Guidance for Industry #187 – Regulation of Genetically Engineered Animals Containing Heritable rDNA Constructs. September 18, 2008.

Guidance for Industry #59 – How to Submit a Notice of Claimed Investigational Exemption in Electronic Format to CVM. (Revised.) January 15, 2008.

Guidance for Industry #73 – Stability Testing of New Veterinary Drug Substances and Medicinal Products, VICH GL3. (Revised.) November 21, 2007.

Guidance for Industry #86 – How to Submit a Notice of Final Disposition of Investigational Animals Not Intended for Immediate Slaughter in Electronic Format to CVM. (Revised.) January 15, 2008.

Guidance for Industry #87 – How to Submit a Notice of Intent to Slaughter for Human Food Purposes in Electronic Format to CVM. (Revised.) January 15, 2008.

Guidance for Industry #88 – How to Submit a Request for a Meeting or Teleconference in Electronic Format to CVM. (Revised.) January 15, 2008.

Guidance for Industry #92 – Impurities In New Veterinary Drug Substances, VICH GL10(R). (Revised.) November 21, 2007.

Guidance for Industry #93 – Impurities in New Veterinary Medical Products, VICH GL11(R). (Revised.) November 21, 2007.

Guidance for Industry #107 – How to Submit a Protocol Without Data in Electronic Format to CVM. (Revised.) January 15, 2008.

Joint Agency Guidances:

Guidance for Industry #190 – Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products (developed in conjunction with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research). February 25, 2008.

Draft Guidance for Industry #194 – Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes (developed in conjunction with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research). August 4, 2008.

Appendix B: Significant New Animal Drug Approvals

The term “Significant Approvals” means the approval of an original or supplemental New Animal Drug Application (NADA) or Abbreviated New Animal Drug Application (ANADA) that required substantial review of safety or effectiveness data (including bioequivalence studies) by CVM and provides for a new chemical entity, a new animal drug product or any of a variety of changes to existing approved NADAs or ANADAs, including additions to the indication section of the label of a new target species, a new significant class of target animals, a new disease indication, a new route of administration, a new tolerance, or withdrawal period.

NEW CHEMICAL ENTITY

CONVENIA (cefovecin sodium)
This original NADA approval provides for the treatment of skin infections (wounds and abscesses) in cats caused by susceptible strains of Pasteurella multocida; and the treatment of skin infections (secondary superficial pyoderma, abscesses and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius and Streptococcus canis (Group G).

NEW INDICATION
EXCEDE (ceftiofur crystalline free acid)
This supplement approval provides a new indication for the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii in beef, non-lactating dairy and lactating dairy cattle.

DRAXXIN (tulathromycin) Injectable Solution
This supplemental approval provides a new indication for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis in beef and non-lactating dairy cattle. This supplemental approval also provides for the addition of Mycoplasma hyopneumoniae to the list of pathogens for the swine respiratory disease (SRD) indication.

PREVICOX (firocoxib) Chewable Tablets
This supplemental approval provides a new indication for the control of post-operative pain and inflammation associated with orthopedic surgery in dogs. A second supplemental approval provides a new indication for the control of postoperative pain and inflammation associated with soft-tissue surgery in dogs.

ORIGINAL GENERIC

PETREM (sevoflurane)
This original ANADA approval provides for induction and maintenance of general anesthesia in dogs. It is a copy of SEVOFLO.

BUTORPHIC (butorphanol tartrate) Injection
This original ANADA approval provides for relief of pain associated with colic in adult horses and yearlings. It is a copy of TORBUGESIC.

CLINDAROBE (clindamycin hydrochloride) Capsules
This original ANADA approval provides for the treatment of skin infections, deep wounds and abscesses, dental infections, and osteomyelitis caused by susceptible strains of organisms as listed on the product label. It is a copy of ANTIROBE Capsules.

VETPROFEN (carprofen)
This original ANADA approval provides for the relief of pain and inflammation associated with osteoarthritis in dogs. It is a copy of RIMADYL caplets.

NEW MAJOR SPECIES

VETSULIN (porcine zinc insulin) Suspension
This supplemental approval provides for use in a new species (cat) for the reduction of hyperglycemia and hyperglycemia-associated clinical signs in cats with diabetes mellitus. This supplemental approval also changes the starting dose in dogs.

BAYTRIL 100 (enrofloxacin) Injectable Solution
This supplemental approval provides for use in a new species (pig) for the treatment and control of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. A second supplemental approval provides for the use of enrofloxacin in female dairy cattle less than 20 months of age.

NEW MINOR SPECIES

TERRAMYCIN 200 for Fish (oxytetracycline dihydrate) Type A Medicated Article
This supplemental approval provides for the control of mortality in freshwater-reared salmonids due to coldwater disease associated with Flavobacterium psycrophilum and mortality in freshwater-reared Oncorhynchus mykiss due to columnaris disease associated with F. columnare.

AQUAFLOR (florfenicol) Type A Medicated Article
This supplemental approval provides for the control of mortality in freshwater-reared salmonids due to furunculosis associated with Aeromonas salmonicida.

VALBAZEN (albendazole) Suspension
This supplemental approval provides for the treatment of adult liver flukes (Fasciola hepatica) in non-lactating goats.

NEW DOSAGE REGIMEN

PIRSUE (pirlimycin hydrochloride) Sterile Solution
This supplemental approval provides for a new dosage regimen-intramammary infusion in lactating dairy cattle once daily (24-hour intervals) for up to 8 consecutive days.

NEW COMBINATION

PANACUR Plus (fenbendazole/ivermectin/praziquantel) Soft Chews
This original combination approval provides for the treatment and control of adult Toxocara canis (roundworm), Ancylostoma caninum (hookworm), Trichuris vulpis (whipworm), and Dipylidium caninum (tapeworm), and for the prevention of heartworm disease caused by Dirofilaria immitis in adult dogs.

NEW FORMULATION

EXCENEL RTU EZ (ceftiofur hydrochloride) Sterile Suspension
This original approval provides for treatment and control of swine respiratory disease in pigs and treatment of bovine respiratory disease, foot rot, and acute postpartum metritis in cattle caused by susceptible strains of organisms as listed on the product label.

NUFLOR Gold (florfenicol)
This supplemental approval provides for the treatment bovine respiratory disease associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef and non-lactating dairy cattle.

AVIAX II (semduramicin) Type A Medicated Article
This original approval provides for the prevention of coccidiosis caused by Eimeria tenella, E. acervulina, E. maxima, E. brunetti, E. necatrix, and E. mitis in broiler chickens.

NEW FEED MIX RULES

SAFE-GUARD (fenbendazole) 20% Type A Medicated Article
The supplement approval provides for the Type A medicated article to be used to manufacture a free-choice liquid Type C medicated feed for the removal and control of various nematode parasites in dairy and beef cattle.

Appendix C: Awards; Center for Veterinary Medicine 2008 Honor Award Recipients*

* In cases in which the award recipients included individuals from CVM and other organizations, only the CVM recipients are mentioned.

FDA AWARD OF MERIT

Steven D. Brynes, Ph.D. - For sustained exemplary review science and continued proficiency in developing regulatory policies and national and international standards concerning critical issues for safe-guarding human food safety.

Elaine A. Johnson - For exceptional performance and leadership in transitioning CVM to a new IT environment while embodying the Agency's core values.

David E. Wardrop, Jr. - For extraordinary contributions in promoting and advancing the vision and goals of CVM and the Agency through successful, expert management and collaborative leadership efforts.

FDA DIVERSITY IN ACTION AWARD

Stephen F. Sundlof, D.V.M., Ph.D. - For demonstrating exceptional creativity, innovation, and diversity in thought and action in implementing the CVM high performance model, motivating employees to reach their fullest potential.

FDA GROUP RECOGNITION AWARD

FDA Science Symposium Planning Committee - For exemplary contributions planning, developing, and executing the 2007 inaugural FDA Symposium Series to enhance professional development and educational opportunities of the FDA community.

Yoko Adachi
Susan J. Bright, D.V.M.
Connie R. Mahon
Ruby Singh, Ph.D.

2008 FDA SCIENTIFIC ACHIEVEMENT AWARDS

EXCELLENCE IN LABORATORY SCIENCE - Shaohua Zhao, D.V.M., M.P.V.M., Ph.D. - For exceptional and outstanding contributions to protecting public health through CVM's food safety surveillance, research, and training programs.

EXCELLENCE IN REVIEW SCIENCE - William J. Burkholder, D.V.M., Ph.D., Randall Anderson Lovell, D.V.M., Ph.D. - For providing scientific support for the unprecedented number of animal and pet food Agency actions concerning products contaminated with melamine and other hazards in 2007.

FDA AWARDS PRESENTED AT THE CVM AWARDS CEREMONY

OUTSTANDING SERVICE AWARD

Susan M. Banks - For extraordinary and substantive contributions to the Center for Veterinary Medicine and the Food and Drug Administration

in meeting critical and complex management initiatives.

Susan J. Bright, D.V.M. - For sustained excellence in post-approval monitoring of new animal drug products, scientific reviews of unapproved marketed animal drugs and devices, label reviews, and pharmocovigilance activities.

Mai X. Huynh - For exceptional contributions to her Team, Office, Center, and Agency on current issues in chemistry, manufacturing, and controls.

Heidi M. Jackson - For outstanding performance and personal initiative in the success of CVM’s financial program activities delivered to HHS, OMB, and Congress.

Patricia A. Ryan - For her superlative support of division programs and her initiative and contributions to new projects such as the volume zero initiative and IT modernization.

Lynn C. Walker, D.V.M. - For outstanding scientific contributions to the review of companion animal new animal drugs.

FDA GROUP RECOGNITION AWARD

CVM Office of Research Institutional Animal Care and Use Committee - For sustained outstanding performance and oversight of the animal research program at CVM’s Office of Research.

Jamie L. Boehmer
Bruce D. Bradley
Annette Cameron
Pak S. Chu, Ph.D
Susan Harper, D.V.M.
Patrick D. McDermott, Ph.D.
Melva Morris
Michael J. Myers, Ph.D.
Jeffrey L. Ward, D.V.M., Ph.D.
CDR Elvira L. Hall-Robinson

GROUP RECOGNITION AWARD

CVM National Antimicrobial Resistance Monitoring System (NARMS) Team - For sustained excellence in monitoring antibiotic resistance in foodborne pathogens from retail meats to better assure the safety of the U.S. food supply.

Jason W. Abbott
Sherry L. Ayers
Mary J. Bartholomew, Ph.D.
Karen E. Blickenstaff
Sonya M. Bodeis-Jones
Peggy J. Carter
Linda L. English
Sharon L. Friedman
Stuart A. Gaines
Althea Glenn
Heather C. Harbottle, Ph.D.
Beth E. Karp, D.V.M., M.P.H.
Patrick F. McDermott, Ph.D.
Shawn D. McDermott
Sadaf Qaiyumi
Laura M. Stets
David G. White, Ph.D.
Shaohua Zhoa, D.V.M., M.P.V.M., Ph.D.
CDR Elvira L. Hall-Robinson

Division of Manufacturing Technologies (DMT) Quality Systems Group - For exceptional teamwork in the design and implementation of quality system concept and principles within the Division of Manufacturing Technologies.

Kristen L. Anderson, Ph.D.
Matthew D. Anderson, Ph.D.
Julie V. Bailey, Ph.D.
Dennis M. Bensley, Jr., Ph.D.
Renee S. Blosser
Stephanie C. Bowman, Ph.D.
Daniel C. Burnette
Jean-Michel Campagne, Ph.D.
Xikui Chen, Ph.D.
Elizabeth P. Cormier, Ph.D.
Bharati R. Dhruva, Ph.D.
Cory D. Evans, Ph.D.
Raafat M. Fahmy, Ph.D.
Scott M. Fontana, Ph.D.
Alem Ghiorghis, Ph.D.
Charles W. Gray, Jr., Ph.D.
Norman R. Gregory
Laura S. Huffman
Gregory W. Hunter, Ph.D.
Mai X. Huynh
Kalatu S. Kamara
Sudesh Y. Kamath, Ph.D.
Jessica R. Lawrence
June Liang, Ph.D.
Charli M. Long, Ph.D.
James K. Nitao, Ph.D.
Charles P. O'Brien, Ph.D.
Michael E. Oehlsen, Ph.D.
Rebecca L. Owen, Ph.D.
Michael J. Popek
J. Kevin Rice, Ph.D.
Robin M. Stone
Faye Y. Wei, Ph.D.
CDR M. Thomas Hendricks

FDA User Fee Negotiation Team - For successful conclusion of the user fee negotiations with industry, thereby exemplifying excellence through collaborative and creative teamwork.

Aila P. Albrecht
Julie V. Bailey, Ph.D.
Dennis M. Bensley, Jr., Ph.D.
Irene Chan Yee Ho
Bernadette M. Dunham, D.V.M., Ph.D.
Petra M. Garosi, P.M.P.
John K. Harshman, Ph.D.
Diane L. Heinz, D.V.M.
Elaine A. Johanson
Lisa M. McGee
David R. Newkirk, Ph.D.
Glenn A. Peterson, Ph.D.
Roxanne K. Schweitzer
Stephen F. Sundlof, D.V.M., Ph.D.
Steven D. Vaughn, D.V.M.
David E. Wardrop, Jr.
Margaret A. Zabriski, Ph.D.

Feed Chromium Working Group - For ongoing and dedicated efforts to ensure safety of animal and human food supplies when chromium substances are added to animal feeds for nutritional purposes.

Michaela G. Alewynse, Ph.D.
Sharon A. Benz, Ph.D.
William J. Burkholder, D.V.M., Ph.D.
Rial A. Christensen, Ph.D.
Karen B. Ekelman, Ph.D.
Devaraya R. Jagannath, Ph.D.
John D. McCurdy, Ph.D.
Julia A. Oriani, Ph.D.
Mark M. Robinson, Ph.D.
Tong Zhou, Ph.D.

Labeling Supplement Working Group - For their exceptional effort in producing the Center's policy on handling labeling supplements as well as creating the policy for a labeling archive (Volume 0).

Charles J. Andres, Ph.D.
Dennis M. Bensley, Jr., Ph.D.
Melanie R. Berson, D.V.M.
Cindy L. Burnsteel, D.V.M.
Petra M. Garosi, P.M.P.
Robin B. Keyser, Ph.D.
Christopher Melluso, D.V.M.
Janis R. Messenheimer, D.V.M.
Dragan Momcilovic, D.V.M., Ph.D.
Arnel B. Peralta, D.V.M.
Sharon L. Ricciardo
Herman M. Schoenemann III, Ph.D.
Mohammad I. Sharar, D.V.M.

Minor Use Minor Species Program Implementation Team - For the efficient and successful implementation of the Minor Use and Minor Species Pre-Indexing Business Processes for the Center for Veterinary Medicine, FDA.

Andrew J. Beaulieu, D.V.M.
Elizabeth A. Canter
Bernadette M. Dunham, D.V.M., Ph.D.
Edward H. Hudson
Elaine A. Johanson
Margaret R. Oeller, D.V.M.
Steven D. Vaughn, D.V.M.
Margaret A. Zabriski, Ph.D.
Contractor Team Members (Alutiiq, LLC.)
Carol E. Goolsby
Josue L. Vega
Contractor Team Members (Booz Allen Hamilton)
Howard Conrad
Irina L. Dergileva
Leonid Drabovsky
Anna A. Filina
Willa V. Fleming
Heather A. Goodman
Shari Graham
Esperanza G. Greene
Jill Kay
Angela C. Loui
Marina Mizina
Vu Nguyen
Sam Rossoshek
Fahad A. Syed

Pre-Approval Inspection Decision Support System (PAIDSS) Working Group - For exceptional creativity and innovation in developing a risk-based decision tool for use in CVM’s Pre-Approval Inspection Program.

Kristen L. Anderson, Ph.D.
Matthew D. Anderson, Ph.D.
Julie V. Bailey, Ph.D.
Dennis M. Bensley, Jr., Ph.D.
Renee S. Blosser
Stephanie C. Bowman, Ph.D.
Daniel C. Burnette
Jean-Michel Campagne, Ph.D.
H. Gregg Claycamp, Ph.D.
Elizabeth P. Cormier, Ph.D.
Bharati R. Dhruva, Ph.D.
Cory D. Evans, Ph.D.
Raafat M. Fahmy, Ph.D.
Scott M. Fontana, Ph.D.
Alem Ghiorghis, Ph.D.
Charles W. Gray, Jr., Ph.D.
Norman R. Gregory
Laura S. Huffman
Gregory W. Hunter, Ph.D.
Mai X. Huynh
Kalatu S. Kamara
Sudesh Y. Kamath, Ph.D.
Jessica R. Lawrence
June Liang, Ph.D.
Charli M. Long, Ph.D.
James K. Nitao, Ph.D.
Charles P. O’Brien, Ph.D.
Michael E. Oehlsen, Ph.D.
Rebecca L. Owen, Ph.D.
Michael J. Popek
J. Kevin Rice, Ph.D.
Robin Stone
Faye Y. Wei, Ph.D.
CDR M. Thomas Hendricks

LEVERAGING/COLLABORATION AWARD - Marilyn N. Martinez Pelsor, Ph.D. - For exceptional performance and leadership in promoting scientific excellence through her collaborations with scientists from throughout the FDA and around the world.

CVM Staff College Team - For the exemplary outreach initiative to enhance collaboration across the Agency and external organizations in the exchange of scientific information via synchronous internet technology.

Stanice L. Cooper
Tina M. Ennis
Connie R. Mahon
Sherri Stephenson-Washington
Karen L. Tracey

Document Room Consolidation Team - For the efficient and successful CVM/CDRH Document Room consolidation effort resulting in cost savings for the Center of Veterinary Medicine, FDA.

Edward H. Hudson
Elaine A. Johanson
Contractor Team Members (Booz Allen Hamilton)
Ali Abbas
Kent McNickle
Marina Mizina
Vikram Pant
Sam Rossoshek
Fahad A. Syed

EXCELLENCE IN EQUITY AWARD -Advisory Committee for Employees with Disabilities - For their exemplary contributions to the Advisory Committee for Employees with Disabilities.

Karen L. Tracey
Loretta A. Walker, D.V.M.

HUMAN CAPITAL INVESTMENT AWARD - Eric S. Dubbin, D.V.M. - For encouraging highly effective work life programs and motivating CVM employees through strong support of Center and Agency workplace culture initiatives.

SCIENTIFIC ACHIEVEMENT AWARDS

CVM OUTSTANDING NEW REVIEWER - Lynne B. Oliver, D.V.M. - For demonstrating an exceptional understanding of the review process and for excellence in reviewing new animal drug applications.

CVM OUTSTANDING SUPPORT SCIENTIST - Michelle Leigh Smith - For outstanding contributions supporting method development for contaminants in animal feed and antiviral drugs in poultry tissue; and sample analysis supporting tissue fluid correlation studies.

CVM DIRECTOR’S HONOR AWARD

Barbara E. Leach - First Place Recipient - For exemplary leadership and performance of CVM’s Management and Administrative activities.

Petra M. Garosi, P.M.P. - Second Place Recipient - For outstanding contributions to the success of the Office of New Animal Drug Evaluation and to the implementation of project management at CVM.

CVM PROJECT MANAGEMENT EXCELLENCE AWARD

Susan J. DeWitt - For outstanding achievements, effectiveness, and commitment to implementation of project management at CVM and for sustained excellence in providing project management support to CVM projects.

Robin M. Stone - For exceptional performance of project management processes and use of the project management tools and techniques for the Division of Manufacturing Technologies.

CVM EXCELLENCE IN MENTORING AWARD

Tracey H. Forfa, J.D. - For extraordinary contribution to all aspects of the Center’s work while at the same time serving unselfishly as a role model and mentor.

Cristina B. Nochetto - For ongoing and continuous excellence in the professional development of fellow employees.

CVM ADMINISTRATIVE EXCELLENCE AWARD

Orton J. Cartwright - For ongoing and continuous excellence in management of the QA/QC Program for CVM/OR and for guidance in developing a program for the Agency.

Lisa M. McGee - For outstanding performance in the success of executing CVM’s financial program activities.

CVM COMMUNICATIONS EXCELLENCE AWARD

Deborah H. Brooks - For meticulous dedication to maintaining and improving the CVM Web site and for exceptional guidance and support to staff as the CVM Librarian.

David N. Heller - For continued excellence in communicating complex scientific information to both technical and general audiences.

CVM SUPPORT STAFF EXCELLENCE AWARD

Holly A. Balance - Administrative - For superior performance in providing extraordinary administrative management support to the Director and employees of the Office of Management, CVM.

Brandi L. Robinson - Administrative - For exemplary leadership and competency in performing the executive assistant duties for the Director of the Office of New Animal Drug Evaluation.

Christopher T. E. Horstkamp - Scientific/Technical - For outstanding leadership as the first and formative facilitator of the ONADE CSO Working Group, and for exemplary leadership in division/office Quality Systems implementation.

Molecular Microbiology Research Team - Scientific/Technical - For exceptional performance in conducting molecular characterization of foodborne pathogens isolated from the CVM NARMS Program.

Jason W. Abbott
Karen E. Blickenstaff
Sharon L. Friedman
Althea Glenn

CVM TEAM EXCELLENCE AWARD

Annual Report Review Module (ARRM) Working Group - For exceptional performance and innovation in the design and implementation of the Annual Report Review Module.

Karen S. Alder
Renee S. Blosser
Elizabeth P. Cormier, Ph.D.
Bharati R. Dhruva, Ph.D.
Scott M. Fontana, Ph.D.
Norman R. Gregory
Mai X. Huynh
Kalatu S. Kamara
Contractor Team Members (Booz Allen Hamilton)
Willa V. Fleming
Shari Graham
Marina Mizina

Bioresearch Monitoring (BIMO) Outreach Team - For excellence in a team outreach exercise for ONADE primary review divisions on the BIMO compliance programs.

Diane T. Bargo
Zollie A. Perry, Ph.D.
George A. Prager
Fredda C. Shere-Valenti
Kathy S. Hemming Thompson
Vernon D. Toelle, Ph.D.

Consolidated Reporting Environment (CRE) Development/Implementation Team -For efficient and successful development and implementation of a robust and flexible reporting system supporting Activity Time Reporting and Activity-Based Costing activities with CVM.

Karen S. Alder
Edward H. Hudson
Elaine A. Johanson
Ann M. Norris
Kimberly A. Sanders
Roxanne K. Schweitzer
Contracting Team Member (Exeter)
Ryan C. Robinson
Contractor Team Members (Booz Allen Hamilton)
Olivier R. Bechouche
Irina L. Dergileva
Willa V. Fleming
Heather A. Goodman
Shari Graham
Angela C. Loui
Kent McNickle
Adrian Suwandi

Prior Notice and Animal Feeds Team - For protecting homeland security by working with FDA’s Prior Notice Center on imported animal feed that may be at risk for deliberate contamination.

William J. Burkholder, D.V.M., Ph.D.
Jack Geltman
George Graber, Ph.D.
Barry H. Hooberman, M.P.H., Ph.D.
Randall A. Lovell, D.V.M., Ph.D.
Phares O. Okelo, Ph.D.
Kim R. Young
CDR Alfred W. Montgomery

World Health Organization-Global Salmonella Surveillance (WHO-GSS) Team - For dedicated service to improve global food safety, through work with the WHO, by building laboratory capacity for public health surveillance in different countries.

Peggy J. Carter
Linda L. English
Patrick F. McDermott, Ph.D.
Shaohua Zhao, D.V.M., M.P.V.M., Ph.D.

OTHER AGENCY AWARDS
(CVM employees included in individual or group recognition awards from other Centers.)
COMMISSIONER’S SPECIAL CITATION

Adulterated Protein Investigations, Analysis, Planning, Scientific Review and Emergency Response Team (Nominated by the Office of Regulatory Affairs) - For exemplary performance to protect the public health from adulterated protein through actions of investigations, sample analyses, method development, assignment planning, emergency response, scientific review, and risk assessment.

Laura C. Alvey
Neal Bataller, D.V.M.
Priscilla Batten
Margarita A. Brown, D.V.M.
Tina M. Burgess
William J. Burkholder, D.V.M., Ph.D.
Jack Geltman
Charles M. Gieseker
David N. Heller
Roderick L. Hudson, Ph.D.
Shannon T. Jordre
Philip J. Kijak, Ph.D.
Teresa L. Koogler
Randall A. Lovell, D.V.M., Ph.D.
Cathie S. Marshall, D.V.M.
Ron A. Miller
CDR Alfred W. Montgomery
Cristina B. Nochetto
Lee Anne Palmer, D.V.M.
Barbara A. Rodgers
Renate Reimschuessel, V.M.D., Ph.D.
Nathan G. Rummel
Kathy S. Hemming Thompson
Marleen M. Wekell, Ph.D.

EU Requirements Update and Molluscan Shellfish Certification Group (Nominated by the Center for Food Safety and Applied Nutrition) - For exceptional effort in responding to new EU requirements for a list of U.S. growing areas for molluscan shellfish and export health certificates for molluscan shellfish/aquaculture finfish in twenty foreign languages.

Kim R. Young

U.S. – China Memorandum of Agreements Team (Nominated by the Office of the Commissioner) - For outstanding teamwork and collaboration in negotiating and concluding two binding agreements intended to advance public health and product safety.

Tracey H. Forfa, J.D.
Daniel G. McChesney, Ph.D.

FDA GROUP RECOGNITION AWARD

FDA Budget Redesign Team (Nominated by the Office of the Commissioner) - For developing a budget request that clearly and effectively articulates FDA budget needs to internal and external audiences.

Heidi M. Jackson
Roxanne K. Schweitzer
Patricia A. Arnwine

FDA Import Safety Working Group (Nominated by the Office of the Commissioner) - For working to ensure the safety of FDA-regulated imported products and successfully contributing to the work of the Interagency Working Group on Import Safety’s Strategic Framework and Action Plan.

Tracey H. Forfa, J.D.
Jack Geltman
Kim R. Young

FDA TOPOFF 4 Exercise Group (Nominated by the Office of the Commissioner) - For exceptional participation in and support for FDA’s Role in TOPOFF 4, the most comprehensive Congressionally mandated full-scale multi-faceted terrorism exercise conducted in the U.S.

Neal Bataller, D.V.M.
William J. Burkholder, D.V.M., Ph.D.
John D. McCurdy, Ph.D.
Christopher Melluso, D.V.M.
CDR Alfred W. Montgomery
Kim R. Young

Import Alert Group (Nominated by the Center for Food Safety and Applied Nutrition) - For outstanding performance in the research, planning, preparation, and clearance of a country-wide import alert that prevented the importation of adulterated aquacultured seafood products into the U.S. from China.

Frances M. Pell
Merton V. Smith, II, Ph.D., J.D.

MARCS CMS Violation Letter Tracking System Implementation Team (Nominated by the Office of Regulatory Affairs) - For superior achievement in the development and implementation of an integrated program for managing violation letters across all Centers, Office of the Chief Counsel, and ORA.

Neal Bataller, D.V.M.
Frances M. Pell
Kim R. Young

Revitalizing ORA: Protecting the Public Health Together in a Changing World Group (Nominated by the Office of Regulatory Affairs) - For dedication in contributing to the development of the final report on “Revitalizing ORA: Protecting the Public Health Together in a Changing World.”

Daniel G. McChesney, Ph.D.

EXCELLENCE IN EQUITY AWARD

Values and Vision Broadcast Team (Nominated by the Office of the Commissioner) - For superior achievement and outstanding development and implementation of the Agency-wide Values and Vision broadcast.

Eric S. Dubbin, D.V.M.

LEVERAGING/COLLABORATION AWARD

Botulism Toxin Response Team (Nominated by the Office of the Commissioner) - For recognition of the superior response to the outbreak of botulinum toxin in canned chili sauce.

Neal Bataller, D.V.M.
William J. Burkholder, D.V.M., Ph.D.
Kathy S. Hemming Thompson
Barbara A. Rodgers
Emily R. Smith

Interagency Risk Assessment Consortium (IRAC) Group (Nominated by the Center for Food Safety and Applied Nutrition) - For interagency collaboration to provide public forums for discussing risk assessment issues related to keeping food and water safe for public consumption.

Barry H. Hooberman, Ph.D., M.P.H.

Pet Food and Animal Feed Contaminant Response Group (Nominated by the Office of the Commissioner) - For superior performance in response to the contamination of pet food and animal feed products.

Laura C. Alvey
Neal Bataller, D.V.M.
Catherine P. Beck
Sharon A. Benz, Ph.D.
William J. Burkholder, D.V.M., Ph.D.
Tracey H. Forfa, J.D.
Jack Geltman
Kristina L. Goddard
David N. Heller
Kathy S. Hemming Thompson
Joanne M. Kla
Vashti D. Klein
Marcia K. Larkins, D.V.M.
Randall A. Lovell, D.V.M., Ph.D.
Cathie S. Marshall., D.V.M.
Daniel G. McChesney, Ph.D.
Cristina B. Nochetto
Renate Reimschuessel, V.M.D., Ph.D.
Barbara A. Rodgers
Jeffrey L. Ward, D.V.M., Ph.D.
Marleen M. Wekell, Ph.D.

OUTSTANDING INTERCENTER SCIENTIFIC COLLABORATION

Tissue Method Development and Implementation Working Group (Nominated by the Office of Regulatory Affairs) - For extraordinary contribution to rapidly developing melamine test methodologies in seafood, studying melamine accumulation in fish, and implementing a seafood testing program for melamine contamination.

Charles M. Gieseker
David N. Heller
Philip J. Kijak, Ph.D.
Cristina B. Nochetto
Renate Reimschuessel, V.M.D., Ph.D.
Nathan G. Rummel
Marleen M. Wekell, Ph.D.

CFSAN TEAM SPIRIT AWARD

FDA Biology Consultation Process Review Team (Nominated by the Center for Food Safety and Applied Nutrition) - For exceptional team spirit in addressing opportunities for process improvements in the conduct of biotechnology consultations for plants bioengineered for food uses.

Michaela G. Alewynse, Ph.D.
Sharon A. Benz, Ph.D.
Rial A. Christensen, Ph.D.
Barry H. Hooberman, Ph.D., M.P.H.
Daniel G. McChesney, Ph.D.
William D. Price, Ph.D.

Appendix D: Publications

CVM Employees are shown in boldface

Aarestrup, F. M., P. F. McDermott, and H. C. Wegener. 2008. Transmission of Antibiotic Resistance from Food Animals to Humans. Campylobacter. (I. Nachamkin, M. Blaser, eds.) American Society for Microbiology (ASM Press), Washington, DC.

Andersen, W. C., S. B. Turnipseed, C. M. Karbiwnyk, S. B. Clark, M. R. Madson, C. M. Gieseker, R. A. Miller, N. G. Rummel, and R. Reimschuessel. 2008. Determination and confirmation of melamine residues in catfish, trout, tilapia, salmon, and shrimp by LC-MS-MS. Journal of Agricultural and Food Chemistry. 56: 4340-4347.

Boehmer, J. L., D. D. Bannerman, K. Shefcheck, and J. L. Ward. 2008. Proteomic analysis of differentially expressed proteins in bovine milk during experimentally induced Escherichia coli mastitis. Journal of Dairy Science. 91:1-13.

Boerlin, P. and D. G. White. 2007. Antimicrobial drug resistance and its epidemiology. In Antimicrobial Therapy in Veterinary Medicine, 4th edition. (S. Giguere, J. F. Prescott, J. D. Baggot, R. D. Walker, and P. M. Dowling, eds.). Blackwell Publishing, Professional.

Chu, P.-S., M. I. Lopez, A. Abraham, K. R. El Said, and S. M. Plakas. 2008. Residue depletion of nitrofuran drugs and their tissue-bound metabolites in channel catfish (Ictalurus punctatus) after oral dosing. Journal of Agricultural and Food Chemistry. 56:8030-8034.

Fahmy, R., D. Danielson, and M. Martinez. 2008. Formulation and Design of Veterinary Tablets. Chapter XX in Pharmaceutical Dosage Forms: Tablets, Volume 2: Rational Design and Formulation, 3rd Edition. (L. L. Augsburger and S. W. Hoag, eds.) Informa Healthcare USA, Inc.

Fleischer S., M. Sharkey, K. Mealey, E. A. Ostrander, and M. Martinez. 2008. “Pharmacogenetic and metabolic differences between dog breeds: their impact on canine medicine and the use of the dog as a preclinical animal model.” AAPS J. 10(1):110-9. Epub. February 15, 2008.

Huynh, M., and M. Martinez. 2008. In vitro and in vivo considerations associated with parenteral sustained release products: A review based upon information presented and points expressed at the 2007 Controlled Release Society Annual Meeting. Journal of Controlled Release. Vol. 129, No. 2.

Kaldhone, P., R. Nayak, A. M. Lynne, D. E. David, P. F. McDermott, C. M. Logue, and S. L. Foley. Characterization of Salmonella enterica serovar Heidelberg from turkey-associated sources. Applied and Environmental Microbiology.2008;74 5038-5046.

Lopez, M. I., J. S. Pettis, I. B. Smith, and P.-S. Chu. 2008. Multiclass determination and confirmation of antibiotic residues in honey using LC-MS/MS. Journal of Agricultural and Food Chemistry. 56: 1553-1559.

Lynne, A. M., B. S. Rhodes-Clark, K. Bliven, S. Zhao, and S. L. Foley. 2008. Antimicrobial Resistance Genes Associated with Salmonella enterica serovar Newport Isolates from Food Animals. Antimicrobial Agents and Chemotherapy. 52:353-356.

Martinez, M., S. Modric, M. Sharkey, L. Troutman, L. Walker, and K. J. Mealey. 2008. The pharmacogenomics of P-glycoprotein and its role in veterinary medicine. J. Vet Pharmacol Ther. (4):285-300.

McDermott, P. F., L. M. McMurry, I. Podglajen, J. L. Dzink-Fox, T. Schneiders, M. P. Draper, and S. B. Levy. 2008. The marC gene of Escherichia coli is not involved in multiple antibiotic resistance. Antimicrobial Agents and Chemotherapy 52(1): 382-383.

McDermott, P. F., J. Simala-Grant, R. D. Walker, and D. E. Taylor. 2008. Antimicrobial Resistance in Campylobacter and Helicobacter. In: Antimicrobial Drug Resistance: Principles for the Clinic and Bench. (D. Mayers, J. Sobel, M. Ouellette, and S. Lerner, eds.) Humana Press.

Miller, R. A., and R. Reimschuessel. 2007. Antimicrobial Drug Use in Aquaculture. Chapter 39. 4th Edition,
Antimicrobial Therapy in Veterinary Medicine
. (Giguere, et al., eds.) pp 593-606.

Miller, R. A., R. Reimschuessel, and M. Carson. 2007. Determination of oxytetracycline levels in rainbow trout serum on a biphenyl column using high-performance liquid chromatography. Journal of Chromatography B. 852:655-658.

Parveen, S., M. Taabodi, T. Mohamed, J. P. Schwarz, T. P. Oscar, J. Harter-Dennis, and D. G. White. 2007. Prevalence and antimicrobial resistance of Salmonella spp. recovered from processed poultry. Journal of Food Protection. 70:2466-2472.

Petri, M., W. Stohl, W. Chatham, W. J. McCune, M. Chevrier, J. Ryel, V. Recta, J. Zhong, and W. Freimuth. 2008. Association of Plasma B Lymphocyte Stimulator Levels and Disease Activity in Systemic Lupus Erythematosus. Arthritis & Rheumatism. Vol. 58, No. 8.

Reimschuessel, R. 2008. Assessing the human health implications of new drugs used in fish farming. Improving farmed fish for the consumer. (Øyvind Lie, ed.) pp 128-156.

Reimschuessel, R., C. Gieseker, R. A. Miller, N. Rummel, J. Ward, J. Boehmer, D. Heller, C. Nochetto, H. De Alwis, N. Bataller, W. Andersen, S.B. Turnipseed, C. M. Karbinwnyk, R. D. Satzger, J. Crowe, M. K. Reinhard, J. F. Roberts, and M. Witkowski. 2008. Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs. American Journal of Veterinary Research. 69: 1217-1228.

Rubin, J., R. D. Walker, K. Blickenstaff, S. Bodeis-Jones, and S. Zhao. 2008. Antimicrobial Resistance and Genetic Characterization of Fluoroquinolone Resistance of Pseudomonas aeruginosa Isolated from Canine Infections. Veterinary Microbiology. 131:164-172.

Rummel, N. and B. Shaikh. 2008. “Determination of albendazole and its metabolites in the muscle tissue of hybrid striped and large mouth bass using liquid chromatography with fluorescence detection.” Journal of AOAC International 9:469-477.

Shaikh, B., N. Rummel, C. Gieseker, C. Cheely and R. Reimschuessel. 2008. “Total radioactive residue depletion of tritium labeled ivermectin in finfish.” Proceedings of the Euro Residue VI Conference: Residues of Veterinary Drugs P2:219-222.

Shaikh, B., N. Rummel, C. Gieseker, and R. Reimschuessel. 2007. Residue depletion of tritium-labeled ivermectin in rainbow trout following oral administration. Aquaculture. 272:192-198.

Sharkey, M., M. Martinez, S. Modric, L. Troutman, and L. Walker. 2008. Understanding Genetic Variability in Dogs and Its Potential Role in Drug Development. FDA Veterinarian. Vol. XXIII, No. 1.

Vila, J., D. G. White, P. F. McDermott, and S. B. Levy. 2008. Bacterial resistance to antimicrobials. Chapter 5. Travelers’ Diarrhea, 2nd Edition. (C. D. Ericsson, H. L. Dupont, and R. Steffen, eds.) BC Decker.

Whichard, J. M., K. Gay, D. G. White, and T. M. Chiller. 2007. Surveillance for antimicrobial resistance among foodborne bacteria: the U.S. approach. Infectious Disease Surveillance. (N. M’ikanatha, R. Lynfield, C. Van Beneden, and H. DeValk, eds.) Blackwell Publishing Professional.

White, D. G. 2008. Laboratory methodologies for bacterial antimicrobial susceptibility testing. Chapter 1.1.10. OIE Manual of Standards for Diagnostic Tests and Vaccines. 6th Edition. Office International des Epizooties.

Yancy, H. F., T. S. Zemlak, J. A. Mason, J. D. Washington, B. J. Tenge, N. T. Nguyen, J. D. Barnett, W. E. Savary, W. E. Hill, M. M. Moore, F. S. Fry, S. C. Randolph, P. L. Rogers, and P. N. Herbert. 2008. The potential use of DNA barcodes in regulatory science: Applications of the regulatory fish encyclopedia. Journal of Food Protection. 71: 210-217.

Zhao, S. 2008. Antimicrobial-Resistant Foodborne Pathogens in Imported Food. Emerging issues in Food Safety: Imported Foods Microbiological Issues and Challenges. (M. P. Doyle and M. C. Erickson, eds.). American Society for Microbiology.

Zheng, J., S. Cui, L. Teel, S. Zhao, R. Singh, A. O’Brien, and J. Meng. 2008. Identification and Characterization of shiga toxin type 2 variants in Escherichia coli isolated from animals, food, and humans. Applied and Environmental Microbiology. 74:5645-5652.

Zheng, J., J. Meng, S. Zhao, R. Singh, Z. Ge, J. G. Fox, and W. Song. 2008. Campylobacter-induced interleukin-8 secretion in polarized human intestinal epithelial cells requires Campylobacter-secreted CDT and TLR-mediated activation of NF-kB. Infection and immunity 76:4498-4508.

Appendix E: Budget and Staffing

 

FY 2008 Enacted BudgetPre-MarketPost-MarketFY 2008 Total(s)
Budget Authority (BA)$31,476,000$32,225,000$63,701,000
User Fee (ADUFA)*$11,523,000 $11,523,000
Total Program Level**$42,999,000$32,225,000$75,224,000
Note: Estimates for the field are not included in the figures above.
Field Activities: Animal Drugs & Feeds
$2,271,000$37,122,000$39,393,000

* ADUFA user fee amount does not include money for Other Activities.
**FY 2008 Supplemental of $6.057M included (CVM $3.963M; Field $2.094M).

 

FY 2008 Enacted Budget
Full Time Equivalents
Pre-MarketPost-MarketFY 2008 Totals(s)
Budget Authority (BA)167151318
User Fee (ADUFA)58 58
Total Program Level225151376

Note: Estimates for the field are not included in the figures above.

Field Activities: Animal Drugs & Feeds

13206219

The FY 2008 Supplemental FTEs are not included (execute in FY 2009).

Scientific & Technical Disciplines at CVM

CVM's total staff is 393

Veterinarians108
Chemists46
Consumer Safety Officers46
Microbiologists40
Biologists36
Other Scientific Disciplines30
Mathematical Statisticians14

Chart does not display 100 percent of CVM Staffing. Data as of 9/30/08.

Appendix F: CVM Performance Goals

Program Results*

√ 1. Implement requirements of FDA Amendments Act within prescribed timeframes.

√ 2. Implement the Food Protection Plan.

√ 3. Implement the Import Safety Action Plan. We made significant progress during FY 2008 in achieving the long term-goals that are included in this goal. For example, we made significant progress toward implementing the multi-Federal agency Import Safety Action Plan, which is designed to enhance the safety of imports entering the United States.

√ 4. Implement FDA’s Strategic Action Plan according to agreed upon project plans.

√ 5. Strengthen Critical Path/Science.

√ 6. Increase access to new medical and food products.

√ 7. Provide for efficient and effective administration of the Animal Drug User Fee Act activities to enhance the review of New Animal Drug Applications and submissions.

√ 8. Reauthorize animal drug user fee program. CVM representatives will co-chair the successful negotiations with industry on a ratified agreement for the reauthorization of ADUFA that included primary responsibility for the development and acceptance of the financial package, and for delivering the completed package to the Department within prescribed timeframes.

√ 9. Negotiate an Animal Generic Drug User Fee program. CVM representatives will co-chair the successful negotiations with industry on a ratified agreement for the authorization of AGDUFA that included primary responsibility for the development and acceptance of the financial package, and for delivering the completed package to the Department within prescribed timeframes.

√10. Antimicrobial resistance. Construct a strategy within Guidance for Industry (GFI) #152 for evaluating critically important antimicrobials to increase the predictability and transparency of the decision-making process.

√11. National Antimicrobial Resistance Monitoring System (NARMS). Conduct the post-approval monitoring of retail meats for antimicrobial resistant foodborne pathogens and commensal organisms under NARMS, and the molecular typing of those pathogens as part of the national PulseNet program.

√12. Pandemic Influenza Preparedness. Support the Department, Agency, and Center objectives in preparation for a possible avian influenza pandemic through development of methods to detect residues in poultry and other bird species of antiviral drugs whose use has been prohibited.

√13. Implement CVM’s Animal Feed Safety System. As described in the section, “Ensuring Food Safety,” we made significant progress during the year in implementing the long-term goals represented in this goal.

√14. Allocate resources to be able to conduct annual targeted BSE inspections of renderers and feed mills processing products containing prohibited materials.

√15. Guide CVM efforts through the FDA Bioinformatics Board decision-making process to ensure CVM business and IT needs are met.

√16. Establish collaboration between CVM and CDRH to leverage existing software and applications to meet CVM electronic submission needs through the FDA/CVM Electronic Document Storage and Review Project.

√17. Strengthen FDA for today and tomorrow. Enhance partnerships to improve how we exchange information with others in the public health community by enhancing our interactions with regulatory agencies in other countries such as EMEU (Europe) and VDD (Canada).

* √ indicates that the goal was achieved

 

ENDNOTES

1Available free through the Federal Citizen Information Center in Pueblo, CO, at http://www.pueblo.gsa.gov/rc/vetnsaids.html

2In January 2009, FDA approved ATryn, an anticoagulant used for the prevention of blood clots in patients who have a rare disease known as hereditary antithrombin deficiency. ATryn is derived from the milk of genetically engineered goats.

3The report is entitled “Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products” [http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/CriticalPathOpportunitiesReports/ucm077262.htm].

4More details on these studies are in the sections on “Increasing the Availability of Safe and Effective Drugs” and “Leveraging Productivity Through Partnerships.”

5CVM Center Leadership Team. Tracey Forfa, Dr. Bernadette Dunham, Cathy Beck, David Wardrop, Dr. Bill Flynn, Dr. Steve Vaughn, Dr. Dan McChesney, Dr. David White, Dr. Eric Dubbin.

6Report No. 110-804 of the House Committee on Energy and Commerce, July 30, 2008, p. 6.

7Id.

8The study of how variations in genetic information affect the response to medications.

9We describe a third drug approval-related critical path study in the section, "Leveraging Productivity Through Partnerships."

10The proposed system would also include animal feeds other than pet food, and would encompass companion animal disease outbreaks.

11Reimschuessel, R., C. Gieseker, R.A. Miller, N. Rummel, J. Ward, J. Boehmer, D. Heller, C. Nochetto, H. DeAlwis, N. Bataller, W. Andersen, S.B. Turnipseed, C.M. Karbinwnyk, R.D. Satzger, J. Crowe, M.K. Reinhard, J.F. Roberts, and M. Witkowski. 2008. Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs.  American Journal of Veterinary Research. 69: 1217-1228.

12Andersen, W.C., S.B. Turnipseed, C.M. Karbiwnyk, S.B. Clark, M.R. Madson, C.M. Gieseker, R.A. Miller, N.G. Rummel, R. Reimschuessel. 2008. Determination and confirmation of melamine residues in catfish, trout, tilapia, salmon, and shrimp by LC-MS-MS. Journal of Agricultural and Food Chemistry. 56:4340-4347.

13Major species are cattle, horses, pigs, chickens, turkeys, dogs, and cats.

14Minor species are all animal species other than humans that are not major species -- for example, aquacultured seafood, sheep, goats, honey bees, zoo animals, ornamental fish, parrots, ferrets, and guinea pigs.

15Members of the fish family Salmonidae, including salmon, trout, and char.

16Oncorhynchus mykiss includes rainbow, steelhead, and redband trout, as well as other related subspecies.

17A serovar (also called serotype) is a group of closely related microorganisms distinguished by a characteristic set of antigens.

18Pertaining to the genome, that is, all of the genetic information possessed by any organism.

19Ruminants are cud-chewing animals that have complex 3-4 chamber stomachs and include cattle, sheep, goats and deer.

20Nonruminants include swine and poultry.

21The remaining 10 percent is found in such cattle parts as the distal ileum of the small intestine, the dorsal root and trigeminal ganglia, and the retina of the eye.

22Cattle that die from disease or injury before they reach the slaughterhouse.

23"Safe FEED - Processed Animal Proteins"

24Bridging studies are designed to develop the correlation between the official approved method and newer, more precise methods. Many older official methods are microbiologically based, while newer chemical methods are based on the detection of a specific chemical entity.  There may not be a direct correspondence between the two methods; bridging studies provide the needed link.

25http://www.fda.gov/RegulatoryInformation/Guidances/ucm125431.htm


26Recombinant DNA technology is a series of procedures used to join together (recombine) DNA segments.

27The DNA construct is the spliced segment of DNA that is introduced into an organism to give the organism new properties.

28The European Food Safety Authority was set up in January 2002, following a series of food crises in the late 1990s, as an independent source of scientific advice and communication on risks associated with the food chain.  It is the keystone of European Union (EU) risk assessment regarding food and feed safety.  (Information taken from the European Food Safety Authority Web site.)

29FDA classifies recalls, according to degree of health hazard posed by the product, into class I, II or III.  Class I recall products present the highest health hazard.

30Transmissible from animals to humans.

31Medical Center Pharmacy v. Mukasey, No. 06-51583 (July 18, 2008)