CVM: Protecting human and animal health 2011 Update Renate Reimschuessel CVM/Office of Research

CVM’s Vision / Mission Mission "Protecting Human and Animal Health"

CVM Organizational Chart Associate Director for Policy and Communications Catherine P. Beck Associate Director for Policy and Communications Catherine P. Beck Associate Director for Management David E. Wardrop, Jr. Associate Director for Management David E. Wardrop, Jr.

CVM’s Core Responsibilities New Animal Drug Review Animal Generic Drug Review Post-approval monitoring of animal drugs and feeds, and marketed animal devices Animal Feed – Human Food – Pet Food -- Protection/Safety Compliance related actions Research to support regulatory decision-making

Companion Animal and Minor Species Medicine ~72 million dogs & 82 million cats ~7 million horses Minor Species include all animals other than the following 7 Major Species: cattle, swine, chickens, turkeys, horses, dogs and cats. CVM is responsible for regulating drugs, devices and food additives used in companion animals (dogs, cats and horses) and minor animal species…

Animal Health and Animal Food Product Safety Animal Drug Manufacturers (300) Feed Manufacturers (6,600) Livestock and Poultry Producers (over 1 million) Specialized Industry/Firms CVM is also responsible for regulating animal drugs, devices and food additives used in food producing animals. From: Given to or used on: 8.5 billion chickens & turkeys 160 million cattle & pigs 11 million sheep & goats Consumed by: 310 million humans in the U.S.

CVM’s Business Priorities Related to foods: Transforming Food Safety Practices – Implementing the Food Safety Modernization Act (FSMA) Animal Biotechnology (genetic engineering and cloning) Unapproved Animal Drugs Bovine Spongiform Encephalopathy (BSE) Illegal Drug Residues in Animal Derived Foods Antimicrobial Resistance (includes the National Antimicrobial Resistance Monitoring System [NARMS]) Turtles (Salmonella sp.) International Activities

Potential for GE Animals Biopharm Research Xenotransplant, scarce cells, tissues, organs Disease resistance Animal derived food products

Genetic Engineering – Bio-pharm “Bio-pharm” animals also present a unique set of challenges. These are animals used to make human biologics or other therapeutics... ( e.g. ATryn – human anticoagulant – a therapeutic protein produced in milk of GE goats.) CVM is still sorting through Compliance requirements. Sponsors are required to submit an application to CVM for review of the animal component. Other product Centers – CBER and CDER will review the human therapeutic. Many sponsors do not realize that they are required to consult with or submit applications to CVM.

Unapproved Animal Drugs There are many unapproved drug products, including those that are compounded outside of what is allowed under AMDUCA, which places a strain on the marketplace These products may have a long history of use but have not gone through the FDA drug approval process to demonstrate safety and effectiveness CVM is currently soliciting comments through a Federal Register Notice that asks for input on potential legal homes for these unapproved drug products. Comment period closed on April 19 th Over 240 comments have been received. The majority of the comments refer to restrictions on compounding and most people are very opposed to the potential of losing the ability to compound from bulk.

BSE Inspections – Shifting Focus This has been a very successful program with a consistent compliance rate of over 90% CVM would now like to shift some of our focus and resources to drug residue work. Most of the Center’s residue-related efforts are currently focused on inspection of Food Safety Inspection Service (FSIS) identified animals presented at slaughter with violative drug residues. Resources currently allow for inspection of less than 50% of the violations reported to the Agency.

Tissue Residues CVM and CFSAN are now participating in an interagency working group with representatives from USDA’s Food Inspection Safety Service (FSIS) and representatives of the Environmental Protection Agency (EPA) to develop a more consistent and collaborative approach to identifying and addressing tissue residues.

Shifting Focus Future efforts will also branch out into a milk sampling assignment which is currently making its way through the clearance process to test the hypothesis of whether poor on farm practices leading to drug residues in tissues are also leading to drug residues in milk.

With leadership and resources from FDA’s Office of International Programs, CVM carried out a number of capacity building projects overseas, including animal drug workshops. Representatives from CVM are key participants in a number of important Codex Alimentarius Activities: Chair of Codex Committee on Residues of Veterinary Drugs in Foods. Participating on Codex Task Force on Antimicrobial Resistance. Participating in Codex Electronic Working Group on Animal Feeding. CVM International Activities

In process to becoming an Official Collaborating Center with the OIE. CVM has ongoing surveillance and Global Monitoring of the Safety of Feed and Feed Ingredients. CVM manages the U.S. NARMS Program and Integration of the World Health Organization – Global Food borne Infections Network. Provides expertise and content for International Capacity Building Project: Training Module on Aquaculture Drug Use CVM International Activities

Purpose of the Aquaculture Training Module: (JIFSAN) Help foreign aquaculture producers understand what drugs & chemicals are allowed (or not) for use in US Includes:Definitions Regulating agencies Laws & regulations Policies & procedures Helps them understand: Food fish vs. nonfood fish Low Regulatory Priority unapproved drugs Extra label use HACCP Import tolerance MRL’s Drugs approved in other countries

Other CVM Challenges -- Antimicrobial Resistance Increasing resistance to antibiotic treatment in bacteria that infect humans raises concerns about the role that drug use in food-producing animals may play in the emergence of resistant bacteria. Monitoring resistance among enteric pathogens in both animals and humans through National Antimicrobial Resistance Monitoring System (NARMS). Provide safe use of antimicrobials in food animals while ensuring that significant human antimicrobial therapies are not compromised or lost Salmonella Enterococcus E. coli

Recent CVM Actions Availability of Draft Guidance (#209) – ‘‘The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals” Advance Notice of Proposed Rulemaking - Veterinary Feed Directive.

NARMS is a national public health surveillance system that tracks antibiotic resistance in foodborne bacteria. National Antimicrobial Resistance Monitoring System (NARMS)

CVM’s OFFICE OF RESEARCH

21 CVM’s Office of Research (OR)  >165 acres  8401 Muirkirk Road  About 70 staff  Large-animal housing and surgery suites  Specialized laboratories  Aquaculture  Pastures  Feed mixing facility  Quarantine facility

OR Organizational Chart Division of Animal and Food Microbiology Director Mark Rasmussen, Ph.D. Division of Animal and Food Microbiology Director Mark Rasmussen, Ph.D.

23 CVM Critical Path Projects 1.Development of analytic approaches and methods for proteomic analysis of milk and the biological fluids 2.Evaluation of the potential trans-placental transfer of genetically engineered material from fetus to dam during pregnancy in ruminants 3.The development of methods to identify and characterize various nanoparticles in biological matrices and determine safety in animal edible tissue and by-products 4.Evolution of multidrug resistant plasmids in Salmonella at the DNA sequence level 5.Application of DNA microarray technology to characterize the inflammatory and immunological responses in swine 6.Development of novel molecular typing strategies for determining source attribution of Salmonella infections 7.Developing alternative ivermectin-sensitive model systems & pharmacokinetics of fexofenadine and loperamide in normal and MDR1 mutant collies 8.Replacing obsolete regulatory methods for veterinary drug residues in animal derived foods including development of equivalence data between new and obsolete methods (bridging study)

24 Premarket/Drug Review Animal Drug Safety and Efficacy (fish disease models) Antimicrobial Resistance Mechanisms (risk assessment) Immunopharmacology (proteomics) Metabolism and Residue Depletion (MUMS) Method Trials (evaluation of reg. methods) Replacement of Obsolete Methods (bridging studies) Microbiological Methods (AST of aquatic pathogens) Pharmacokinetics/Pharmacodynamics (spp. differences) Pharmacogenomics (predicting safety) Ensuring the safety and efficacy of drugs for animals, while protecting the food supply is a core mission for CVM.

25 Compliance Drug Residue Methods Method Trials and Validation Pharmacokinetics and Residue Depletion Screening Tests Incursion Services Supporting CVM agency, state and federal efforts to ensure that animal drugs are not misused

OR Organizational Chart Division of Animal and Food Microbiology Director Mark Rasmussen, Ph.D. Division of Animal and Food Microbiology Director Mark Rasmussen, Ph.D.

Vet-LRN Veterinary Laboratory Response Network What is the mission? To promote human and animal health by collaborating with veterinary diagnostic laboratories to provide scientific information, to build laboratory capacity and to train scientists investigating CVM regulated products ( animal feeds/animal drugs )

Vet-LRN Veterinary Laboratory Response Network How: Develop infrastructure through Communications network, Cooperative agreement/Grants/Contracts, Training/Proficiency exercises

Vet-LRN Veterinary Laboratory Response Network And WHY do we need it?

Contact FDA Animal is sick Lab work Vet bills Was it the food?

What does CVM want? Veterinary Records

What does CVM want? Veterinary Records Collect Feed/Drug samples

What does CVM want? Veterinary Records Collect Feed/Drug samples More Tests? Who Pays? Necropsy? Histopathology?

Need a system to help investigate potential pet/livestock food/medicine related disease

Need a system to help investigate potential pet/livestock food related disease CVM is developing a new network similar to the FERN system (smaller)

Where does Vet-LRN fit in? We don’t need to re-invent the wheel Small program 2 People in Office of Research, 1 Person in Office of Surveillance and Compliance 1 Contractor

March 2011 stakeholder input Veterinary Diagnostic Laboratories Develop contacts with CVM Describe capabilities Describe needs

Who all is interested?

What makes Vet-LRN unique? Vet-LRN diagnostic labs will help with the surveillance of veterinary cases unlikely to come into food testing laboratories on a routine basis. Vet-LRN will analyze diagnostic samples from livestock and companion animals exposed to adulterated/contaminated food and drugs Vet-LRN wants to work with the other networks, not in isolation Vet-LRN will fund projects outside the current mission of other networks