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OIE Collaborating Centre Reports

Activities in 2012

Title of Collaborating Centre: OIE Collaborating Centre for Veterinary Drug Regulatory Programmes

Address of Collaborating Centre: Center for Veterinary Medicine (CVM), Food and Drug Administration, Department of Health and Human Services, United States of America, 7519 Standish Place, HFV-1, Room 177, Rockville, Maryland, 20855, USA

Tel.: 240-276-9300

Fax: 240-276-9030

e-mail address: [email protected]

website: http:www.fda.gov/AnimalVeterinary/default.htm

Name of Director of Institute Dr. Bernadette M. Dunham (Responsible Official):

Name (including Title and Dr. Merton V. Smith Position) of Head of the Collaborating Centre (formally OIE Contact Point):

Name (including Title and Jon F. Scheid, Position) of writer of this report International Communications Manager (if different from above)

Annual reports of OIE Reference Centres, 2012 1 Veterinary Drug Regulatory Programmes

Summary of activities specifically related to the mandate of OIE Collaborating Centres

1. Activities as a centre of research, expertise, standardisation and dissemination of techniques within the remit of the mandate given by the OIE

Dr. Kathleen Jones of CVM’s Animal Biotechnology Interdisciplinary Group (ABIG) chaired the Organization of Economic Cooperation and Development (OECD) Task Force for the Safety of Novel Foods and Feeds in Paris in March 2012.1 Ms. Jeanette Murphy, an expert in the area of feed safety of genetically engineered plant material and representing ABIG, also attended the meeting. The Task Force works toward the harmonization of approaches to the safety assessments of novel foods and feeds, including those derived from GE organisms and other new technologies.

Members of CVM’s ABIG participated in the OECD Working Group for the Harmonization of Regulatory Oversight in Biotechnology. Dr. Larisa Rudenko co-chaired the drafting group for the Biology of Atlantic Salmon Consensus Document, and Dr. Eric Silberhorn was the lead author for the consensus document. The document is expected to progress to OECD review in 2013.

As part of a joint delegation comprised of representatives from the U.S. Department of Agriculture’s Foreign Agricultural Service and CVM, Dr. Larisa Rudenko and Dr. Harlan Howard of ABIG visited the People’s Republic of China for an exchange of information on the state of research and development of genetically engineered livestock and fish. These CVM experts led discussions with the Chinese delegations on the agency’s risk-based approaches to the regulation of genetically engineered animals. Members of the Chinese delegations discussed their research on genetically engineered animals, and gave an overview of the regulatory processes applicable to genetically engineered animals in China. The U.S. delegation also met with members of the Chinese Academy of Sciences from four institutions who are involved with genetically engineered animal research.

In March, CVM announced the availability on its website of its National Antimicrobial Resistance Monitoring System (NARMS) Retail Meat Annual Report with data collected in 2010. The main purpose of the NARMS retail meat surveillance program is to monitor antimicrobial resistance among foodborne Salmonella, Campylobacter, Enterococcus, and Escherichia coli in raw, unprocessed retail meats. The development of antimicrobial resistance in these organisms may be influenced by the use of antimicrobial agents in food animals. These data can be combined with data from slaughter plants and on-farm studies for insights into the emergence and spread of antimicrobial resistance in foodborne bacteria originating from food animals.

In June, Dr. Marilyn Martinez, Senior Scientist in the Office of New Animal Evaluation, served as the chair of the VICH Expert Working Group on Bioequivalence, which met in Brussels. She was accompanied by Dr. Katherine Weld of the Office of New Animal Drug Evaluation. The Working Group is developing international guidelines to describe the protocol development and data analysis of blood level bioequivalence trials conducted in support of certain veterinary drug approvals.

In June, Dr. David White, Director of the Office of Research, attended the OIE ad hoc Group on Antimicrobial Resistance in Paris to assist in OIE’s global efforts to harmonize efforts to address the issue of antimicrobial resistance.

In July, CVM announced the availability of the NARMS Enteric Bacteria 2010 Executive Report, which summarizes in an integrated format NARMS data on non-typhoidal Salmonella and Campylobacter isolates recovered in 2010 from human clinical cases, retail meats, and food animals at Federally inspected slaughter and processing plants. In addition, the report includes data on E. coli isolates recovered from retail meats and chickens.

In July, Dr. Shaohua Zhao of the Office of Research attended a meeting of the WHO Expert Consultation in collaboration with FAO and OIE to develop an international approach to address the issue of campylobacteriosis, The consultation was held in Utrecht, the Netherlands. The purpose of the consultation was to review progress

1 FDA and CVM review and approve genetically engineered animals under a regulatory framework that is based on the U.S. legal authority to review and approve new animal drugs. While in many other countries these products are not considered as new animal drugs, activities in this area are being reported here as part of the activities of the CVM OIE Collaborating Centre for Veterinary Drug Regulatory Programmes.

2 Annual reports of OIE Reference Centres, 2012 Veterinary Drug Regulatory Programmes

concerning the development of techniques to control of Campylobacter in the food chain and to develop a pathway to reduce the burden of disease and health impact, including consideration of antimicrobial resistance.

In August, Dr. Michael Oehlsen of CVM’s International Programs Team, Dr. Steve Yan of CVM’s Office of New Animal Drug Evaluation, and Dr. Don Prater of FDA’s Office of International Programs organized and presented a workshop in San Jose, Costa Rica, for a number of Latin American countries covering the recently developed Codex antimicrobial resistance guidelines. The Codex Task Force on Antimicrobial Resistance completed in 2011 the development of recommendations that provide guidance on assessing and managing the risk of antimicrobial resistance as a result of the use of antimicrobial drugs in veterinary medicine. The three-day workshop was attended by representatives from 16 Latin American countries. The Antimicrobial Resistance Commission established by the Government of Costa Rica had invited the CVM/FDA team to participate and make presentations.

2. Proposal or development of any procedure that will facilitate harmonisation of international regulations applicable to the surveillance and control of animal diseases, food safety or animal welfare

3. Networking

a) Maintenance of a network with other OIE Collaborating Centres designated for the same specialty, and

CVM hosted an extended visit and training session of several weeks for Dr. Nao Nakajima, Section Chief, Planning and Coordination Division, National Veterinary Assay Laboratory (NVAL), Ministry of Agriculture, Forestry and Fisheries, Japan. The training included an in depth review of the process CVM uses in its review of animal drugs. This activity supports the on-going cooperation between CVM and NVAL in their roles as OIE Collaborating Centres in the area of veterinary drug regulation.

b) Should the need arise, maintenance of a network with Collaborating Centres in other disciplines

Dr. Bettye Walters of CVM’s International Programs Team and Dr. Cindy Burnsteel of CVM’s Office of New Animal Drug Evaluation accompanied Dr. Rick Hill of the U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS), Veterinary Services, Center for Veterinary Biologics at a CAMEVET Meeting in Sao Palo, Brazil, during October. The APHIS Center for Veterinary Biologics participates as part of the OIE Collaborating Centre for Diagnosis of Animal Diseases and Vaccine Evaluation for the Americas.

4. Placement of expert consultants at the disposal of the OIE

Dr. Pat McDermott of CVM’s Office of Research served on the OIE Ad Hoc Group on Antimicrobial Resistance and participated in the meeting of this group held in Paris in July. The Ad Hoc Group was able to finalize two chapters of the OIE Terrestrial Animal Health Code during the meeting that focused on the prudent use of veterinary antimicrobials guideline and risk assessment.

5. Provision of scientific and technical training, within the remit of the mandate given by the OIE, to personnel from OIE Member Countries

CVM hosted an extended visit and training session of several weeks for Dr. Nao Nakajima, Section Chief, Planning and Coordination Division, National Veterinary Assay Laboratory, Ministry of Agriculture, Forestry and Fisheries, Japan. The training included an in depth review of the process CVM uses in its review of animal drugs.

6. Organisation of scientific meetings on behalf of the OIE

Dr. Bettye Walters of the International Programs Team was a presenter at the Regional Seminar for OIE National Focal Points for Veterinary Products in Vienna, Austria, in November. The seminar was organized for representatives from Eastern European countries. Dr. Walters made presentations on VICH, the establishment of Maximum Residue Limits, the animal drug residue monitoring plans, and animal drug withdrawal periods. In addition, she led workshops on the establishment of residue monitoring plans and on monitoring of antimicrobial resistance and quantities of antimicrobials used in animals.

In May, Dr. Walters and Dr. Margarita Brown of the Division of Veterinary Product Safety in the Office of Surveillance and Compliance participated in OIE’s National Focal Points for Veterinary Products Seminar in Bangkok, Thailand. Both experts gave presentations on several topics including pharmacovigilance and the establishment of Maximum Residue Limits.

Dr. Bettye Walters organized a Regional Seminar for OIE National Focal Points for Veterinary Products in Mombasa, Kenya, in March 2012. Dr. Walters and Dr. Merton Smith of CVM’s International Programs Team, Dr. Steve Vaughn, Director of CVM’s Office of New Animal Drug Evaluation, Dr. Margarita Brown of the Division of Veterinary Product Safety in the Office of Surveillance and Compliance, and Dr. Rick Hill, of the U.S. Department of Agriculture’s Center for Veterinary Biologics, presented an overview of governance of veterinary medicinal products. Dr. Smith also made a presentation about the structure and organization of the VICH. He described the elaboration of VICH guidelines and the VICH’s program of global outreach. Dr. Vaughn and Dr. Hill presented information about the control of drugs and vaccines, including information about inspection systems, monitoring plans, distribution of vaccines, and counterfeiting. Dr. Margarita Brown of CVM’s Division of Veterinary Drug Safety led a workshop about pharmacovigiliance of veterinary drugs. Dr. Walters made a presentation about the responsible use of veterinary products, and led a workshop that featured a practical exercise in the establishment of a drug residue monitoring plan.

7. Coordination of scientific and technical studies in collaboration with other laboratories, organisations or collaborating centres

Dr. Pat McDermott of CVM’s Office of Research led a subcommittee of the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance that during 2012 completed a document on harmonized approaches to integrated surveillance systems using elements of mature monitoring programs such as FDA’s NARMS. The document provides guidance to countries as they build laboratory capacity and implement integrated monitoring programs.

8. Publication and dissemination of any information within the remit of the mandate given by the OIE that may be useful to Member Countries of the OIE

Tissue/fluid correlation study for Chiesa OA, Li H, Kijak P, et al. June 2012, Issue 3, Vol. J Vet Pharmacol the depletion of sulfadimethoxine 35, pages 249-258 Therap in bovine kidney, liver, plasma, urine, and oral fluid. The scientific basis for Martinez MN and Fahmy R. March 2012, Vol. 35, J Vet Pharmacol establishing solubility criteria for pages 81-86 Therap veterinary species Study of physicomechanical Lin Z, Qu H, Kothari B, Chokshi October 2012 AAPS Annual properties of aqueous R, Carlin B, Fahmy R, and Hoag Meeting, ethylcellulose dispersion films SW Chicago, IL during the curing process Should licking behavior be Toutain PL, Modric S, Bousquet- April 2012, Vol. 35, J Vet Pharmacol considered in the bioavailabilty Mélou A, Sallovitz JM, Lanusse pages 39-43 Therap evaluation of transdermal C products? Quality by Design and the Fahmy R, Danielson D, and October 2012, book Animal Health Development of Solid Oral Martinez M. chapter Drug Delivery Dosage Forms Quality-by-Design I: Application Fahmy R, Kona R, Dandu R, Xie 2012 AAPS

4 Annual reports of OIE Reference Centres, 2012 Veterinary Drug Regulatory Programmes of Failure Mode Effect Analysis W, Claycamp G, and Hoag SW PharmSciTech (FMEA) and Plackett-Burman design of experiments in the identification of _main factors_ in the formulation and process design space for roller compacted ciprofloxacin hydrochloride immediate release tablets. Probability concepts in quality Claycamp HG Jan-Feb 2012, Vol. 66, PDA J Pharm risk management pages 78-89 Sci Technol Oxytetracycline pharmacokinetics Miller RA, Pelsor FR, Kane AS, June 2012, Issue 2, Vol. J Aquat Anim in rainbow trout during and after and Reimschuessel R 24, pages 121-128 Health an orally administered medicated feed regimen Neurotoxic effects of ivermectin Orzechowski KL, Swain MD, September 2012, Issue 9, Am J Vet Res administration in genetically Robl MG, Tinaza CA, Swaim Vol. 73, pages 1477- engineered mice with targeted HL, Jones YL, Myers MJ, and 1484 insertion of the mutated canine Yancy HF ABCB1 gene Marker Residue Determination of Shaikh B, Rummel N, Yu D, March 2012, website J Agric Food Tritium-Labeled Ivermectin in the Gieseker C, Evans E, Hasbrouck Chem Muscle of Aquacultured N, Reimschuessel R. Largemouth Bass, Hybrid Striped Bass and Yellow Perch following Oral Treatment In vivo characterization of Peters SM, Yancy HF, Deaver C, August 2012, Issue Vet Immunol inflammatory biomarkers in swine Jones YL, Kenyon E, Chiesa OA, 40972, Vol. 148, pages Immunopatho and the impact of flunixin Esparza J, Screven R, Lancaster 236-242 meglumine administration V, Stubbs III, JT, Yancy M, Wiesenfeld PL, and Myers MJ In vitro binding of enrofloxacin in Ahn Y, Linder SW, Veach BT, February 2012, Issue 1, Regul Toxicol human fecal slurries Steve Yan S, Haydée Fernández Vol. 62, pages 74-84 Pharmacol A, Pineiro SA, Cerniglia CE Introduction to the bioequivalence Martinez MN and Hunter RP March 2012, Vol. 35, J Vet Pharmacol theme issue pages 1-2 Therap Eudragit® RS PO/RL PO as rate- Dave VS, Fahmy R, Bensley D, January 2012, book Drug controlling matrix-formers via and Hoag SW Development roller compaction: Influence of and Industrial formulation and process variables Pharmacy on functional attributes of granules and tablets Estimating product Claxton R, Cook J, Endrenyi L, March 2012, Vol. 35, J Vet Pharmacol bioequivalence for highly variable Lucas A, Martinez MN, and pages 11-16 Therap veterinary drugs Sutton SC. Effects of Preprocessing Methods Ashour A, Fahmy R, and Hoag October 2012 AAPS Annual In Near Infrared Spectral Data for SW Meeting, PLS Modeling of Chemical and Chicago, IL Physical Properties of Intact Pharmaceutical Tablets Effect of Humidity on the Coating Kothari BH, Jancsik B, Fahmy R, October 2012 AAPS Annual Efficiency of Ciprofloxacin HCl and Hoag SW Meeting, Controlled Release Chicago, IL Multiparticulate Beads Effect of Coating Processing Kothari BH, Ashour A, Fahmy R, October 2012 AAPS Annual Parameters on the Dissolution Moore C, and Hoag SW Meeting,

Profiles of Ciprofloxacin HCl Chicago, IL Controlled Release Multiparticulate Beads Drug solubility classification in Martinez MN and Papich MG March 2012, Vol. 35, J Vet Pharmacol the dog pages 87-91 Therap Drug solubility classification in Martinez MN and Apley MD March 2012, Vol. 35, J Vet Pharmacol the bovine pages 93-97 Therap Development and Validation of a Hepburn S, Lin Z , Wang JB , October 2012 AAPS Annual Stability-indicating HPLC Fahmy R , and Hoag SW Meeting, Method for the Estimation of L- Chicago, IL tetrahydropalmatine in a Capsule Dosage Form Demonstrating bioequivalence Bermingham E, DelCastillo JRE, March 2012, Vol. 35, J Vet Pharmacol using clinical endpoint studies Lainesse C, Paloske K, and pages 31-37 Therap Radecki S Considerations for extrapolating Modric S, Bermingham E, Heit April 2012, Vol. 35, J Vet Pharmacol in vivo bioequivalence data across M, Lainesse C, Thompson C pages 45-52 Therap species and routes A systematic review of the safety Hope E. Baird-Heinz, A'ndrea L. March 2012, Issue 6, JAVMA of potassium bromide in dogs. Van Schoick, Francis R. Pelsor, Vol. 240, pages 705-715 Lauren Ranivand, Laura L. Hungerford Assessing product bioequivalence Gehring R and Martinez MN March 2012, Vol. 35, J Vet Pharmacol for extended-release formulations pages 3-9 Therap and drugs with long half-lives Antimicrobial Drug Resistance in Tadesse DA, Zhao S, Tong E, May 2012, Issue 5, Vol. Emerging Escherichia coli from Humans Ayers S, Singh A, Bartholomew 18, pages 741-749 Infectious and Food Animals, United States, MJ, McDermott PF. Diseases 1950_2002 Animal Drugs: Factors Martinez MN, Antonovic L, 2012, book chapter 345 Encyclopedia of Influencing their Development Dunham B, Fahmy R, Gilbert J, Pharmaceutical and Use Hungerford L, Modric S, Papich Science and M, Smith M, Yan SS Technology, Editor:Swarbrick A Determinative and Feng S, Chattopadhaya C, Kijak June 2012, Vol. 898, Journal of Confirmatory Method for P, Chiesa O, and Tall EA pages 62-68 Chromatography Ceftiofur Metabolite B Desfuroylceftiofur Cysteine Disulfide in Bovine Kidney by LC-MS/MS

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