FOOD ANIMAL RESIDUE AVOIDANCE DATABANK (FARAD) VMCVM COMPONENT

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: OTHER GRANTS
• Reporting Frequency: Annual
• Accession No.: 1017267
• Grant No.: 2018-41480-28808
• Cumulative Award Amt.: $150,000.00
• Proposal No.: 2018-05989
• Project Start Date: Sep 1, 2018
• Project End Date: Aug 14, 2020
• Grant Year: 2018
• Program Code: [FARAD]- Food An. Res. Avoidance Database,FARAD

Recipient Organization
VIRGINIA POLYTECHNIC INSTITUTE
(N/A)
BLACKSBURG,VA 24061

Performing Department
Biomedical Sciences & Pathobio

Non Technical Summary
The Food Animal Residue Avoidance Databank (FARAD) program is a chemical food safety program designed to provide up-to-date pharmacokinetic information to veterinarians in order to determine withdrawal times for extralabel drug use in food animal species. The program has been in existence for more than 30 years and is a collaborative effort by pharmacology specialists at the veterinary colleges at North Carolina State University, University of California, Davis, University of Florida, Kansas State University and Virginia Tech. FARAD has a direct impact on the production of safe foods of animal origin through the prevention and mitigation of violative chemical (drug, pesticide, natural toxins, and environmental contaminant) residues in food animal products. Each of the five FARAD centers has expertise for delivery of the required information which eliminates redundancies and allows for collaboration of talents unique to the field of veterinary pharmacokinetics research and related database management. The primary role of FARAD at Virginia Tech will be to respond to drug residue cases in livestock from food animal veterinarians and extension specialists, and to provide research support that attempts tovalidate estimated withdrawal intervals following extralabel drug use. FARAD will also enable Virginia Tech to train new residents in Veterinary Clinical Pharmacology and strengthen relationships with the FDA Center for Veterinary Medicine through resident and student externships.

Animal Health Component

80%

Research Effort Categories

Basic

20%

Applied

80%

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
711	3260	1180	10%
711	3320	1180	20%
711	3210	1180	20%
711	3410	1180	20%
711	3510	1180	10%
711	3820	1180	10%
711	3610	1180	10%

Knowledge Area
711 - Ensure Food Products Free of Harmful Chemicals, Including Residues from Agricultural and Other Sources;

Subject Of Investigation
3610 - Sheep, live animal; 3210 - Egg-type chicken, live animal; 3320 - Meat, beef cattle; 3510 - Swine, live animal; 3260 - Poultry meat; 3820 - Goats, meat, and mohair; 3410 - Dairy cattle, live animal;

Field Of Science
1180 - Pharmacology;

Keywords

extralabel drug use

food animal

food safety

pharmacology

Goals / Objectives
VMCVM Regional Access Center Work Plan: During the 2018-2019 project year.The regional center at VMCVM will continue to support the essential tasks of the national FARAD program outlined below, provide pharmacokinetic services to all FARAD sites, and continue developing pharmacokinetic model tools that allow FARAD responders to fully utilize published studies to avoid meat and milk violative residues in food animals. The primary focus areas of the VMCVM FARAD component for 2018 - 2019 are as follows: (1) strengthen the response team via the hiring of a veterinary pharmacology resident and graduate student (Dr. Mercer) and, in collaboration with NCSU and UC Davis, provide drug and chemical residue management expertise to veterinarians by answering telephone and internet inquiries; (2) collaborate with NCSU, KSU, UC Davis, and University of Florida, to validate (via in vivo studies) many of our computational estimates of a safe withdrawal time.Respond to drug and chemical residue cases The VMCVM FARAD Regional Access Center will continue in collaboration with NCSU and UC-Davis FARAD Regional Access Center to answer residue avoidance inquiries. This service will require the veterinary clinical pharmacology expertise of Dr. Jennifer Davis and a Veterinary Pharmacology Resident/PhD student, Dr. Melissa Mercer (DVM, MS). Dr. Mercer will be responsible for daily management of cases at VMCVM. This represents a new response center and will facilitate the accuracy and timeliness of FARAD's response to as many as 70 cases a week. VMCVM will also collaborate and contribute to writing timely FARAD Digests that focus on the management of the more common drug residue scenarios facing food animal veterinarians. We will collaborate in outreach programs to producer groups and veterinary specialty groups such as AVMA, AABP, AAVPT. Dr. Davis is the current Secretary of AAVPT and is uniquely positioned to ensure continued collaboration between AAVPT and FARAD. The VMCVM also has a long-standing relationship with the FDA Center for Veterinary Medicine through providing externship opportunities for students and potentially FARAD graduate students/residents. Our proximity to the FDA facilities is a great advantage in this area.Pharmacokinetic TrialsVMCVM will collaborate with NCSU and UC-Davis to obtain in vivo data to validate FARAD approved withdrawal intervalcommendations. his will be accomplished by participation in in vivo pharmacokinetic studies in food producing animals to determine detection times of drug in products such as eggs, milk or tissues. VMCVM has a fully equipped Pharmacology/Toxicology laboratory that will complement facilities currently in use at NCSU and UC-Davis. Animals and animal facilities are also available through the VMCVM.

Project Methods
In order to carry outits mission, the FARAD team collates, analyzes and interprets the most up-to-date information and uses that unique data repository to provide accurate and timely expert advice to assist veterinarians who are faced with situations that could cause unsafe chemical residues in human food products.VT will accomplish this bycollecting pharmacokinetic data and analyzing it to validate drug withdrawal times. In addition, FARAD maintains and provides an array of complete information resources for veterinarians, extension specialists, farmers, regulatory personnel and others who are the stewards of our nation's expansive commercial food animal industries and the growing number of small backyard livestock operations.VT will accomplish this by providing outreach extension to veterinarians and producers viatelephone calls in internet inquiries.

Progress 09/01/18 to 08/31/20

Outputs
Target Audience:The primary goal for VMCVM FARAD is to provide outreach and support to veterinarians on issues of extralabel drug use withdrawal intervals. This is done online and via phone submission. VMCVM FARAD responds tocalls for approximately 17 weeks out of a 52 week period. At an average of 50-75 calls per week, this results in asignificant benefit to veterinarians, our target audience. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Dr. Davis is in charge of organizing and presiding over training workshops for new FARAD call responders at VMCVM,UC Davis and NC State University. The initial workshop was held in September of 2018 and another in July2019. How have the results been disseminated to communities of interest?All call responses go directly to the veterinarian of record on the case. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The VMCVM Regional Access Center has been active since September 2018. Dr.s. Mercer and Davis have been responsible for answering calls for a third of this period, as well as consulting on calls and cases during the remaining 2/3 of the time. Dr. Davis has been in charge of updating and refining the FARAD Responder's manual and hosting responder training meetings for allnew responders. We have completed sampling and sample analysis for a pharmacokinetics study title 'Pharmacokinetics of multiple dose flrofenicol in nursing goats and kids.' Dr. Mercer has completed an initial draft of a FARAD Digest on Rodenticide exposure in Food Animals.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: 5. M Li, Y Cheng, JT Chittenden, RE Baynes, LA Tell, JL Davis, TW Vickroy, JE Riviere, Z Lin. Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population?based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration. Archives of Toxicology. 2019. Jul;93(7):1865-1880. DOI: 10.1007/s00204-019-02464-z
• Type: Journal Articles Status: Published Year Published: 2019 Citation: D Mzyk, C Bublitz, M Martinez, JL Davis, G Smith, R Baynes. Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves. PLOS ONE. 2019 Jun 24;14(6):e0218864. DOI: 10.1371/journal.pone.0218864
• Type: Journal Articles Status: Published Year Published: 2019 Citation: KL Martin, MO Clapham, JL Davis, RE Baynes, Z Lin, TW Vickroy, JE Riviere, LA Tell. Extra-label Drug Use in Wildlife and Game Animals. Journal of the American Veterinary Medical Association. 2019; 255 (5): 555-568.

Progress 09/01/18 to 08/14/20

Outputs
Target Audience:The primary goal for VMCVM FARAD is to provide outreach and support to veterinarians on issues of extralabel drug use withdrawal intervals. This is done online and via phone submission. VMCVM FARAD responds tocalls for approximately 17 weeks out of a 52 week period. At an average of 50-75 calls per week, this results in asignificant benefit to veterinarians, our target audience. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Dr. Davis is in charge of organizing and presiding over training workshops for new FARAD call responders at VMCVM,UC Davis and NC State University. The initial workshop was held in September of 2018 and another in July2019. How have the results been disseminated to communities of interest?All call responses go directly to the veterinarian of record on the case. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? The VMCVM Regional Access Center has been active since September 2018. Dr.s. Mercer and Davis have been responsible for answering calls for a third of this period, as well as consulting on calls and cases during the remaining 2/3 of the time. Dr. Davis has been in charge of updating and refining the FARAD Responder's manual and hosting responder training meetings for allnew responders. We have completed sampling and sample analysis for a pharmacokinetics study title 'Pharmacokinetics of multiple dose flrofenicol in nursing goats and kids.' Dr. Mercer has completed an initial draft of a FARAD Digest on Rodenticide exposure in Food Animals.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: 5. M Li, Y Cheng, JT Chittenden, RE Baynes, LA Tell, JL Davis, TW Vickroy, JE Riviere, Z Lin. Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population?based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration. Archives of Toxicology. 2019. Jul;93(7):1865-1880. DOI: 10.1007/s00204-019-02464-z
• Type: Journal Articles Status: Published Year Published: 2019 Citation: D Mzyk, C Bublitz, M Martinez, JL Davis, G Smith, R Baynes. Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves. PLOS ONE. 2019 Jun 24;14(6):e0218864. DOI: 10.1371/journal.pone.0218864
• Type: Journal Articles Status: Published Year Published: 2019 Citation: KL Martin, MO Clapham, JL Davis, RE Baynes, Z Lin, TW Vickroy, JE Riviere, LA Tell. Extra-label Drug Use in Wildlife and Game Animals. Journal of the American Veterinary Medical Association. 2019; 255 (5): 555-568.

Progress 09/01/18 to 08/31/19

Outputs
Target Audience:The primary goal for VMCVM DARAD is to provide outreach and support to veterinarians on issues of extralabel drug use withdrawal intervals.This is done online and via phone submission. Since funding, the VMCVM FARAD has responded to calls for approximately 15 weeks out of a 43 week period. At an average of over 300 calls per week, this results in a significant benefit to veterinarians, our target audience. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Dr. Davis is also in charge of organizing and presiding over training workshops for new FARAD call responders at VMCVM, UC Davis and NC State University. The initial workshop was held in September of 2018 and another is scheduled for July 2019. How have the results been disseminated to communities of interest?All call responses go directly to the veterinarian of record on the case. What do you plan to do during the next reporting period to accomplish the goals?We will continue to respond to veterinary ELDU inquiries. The pharmacokinetic trials will be scheduled within the next 12 months period (to coincide with calving, lambing, kidding and maximal milk porduction in farm animals).

Impacts
What was accomplished under these goals? The VMCVM Regional Access Center has been active since September 2018. Dr.s. Mercer and Davis have been responsible for answering calls for a third of this period, as well as consulting on calls and cases during the remaining 2/3 of the time. Dr. Davis has been in charge of updating and refining the FARAD Responder's manual and hosting responder's meetings for all call responders every three months. Due to a delay in funds accesibility, the pharmacokinetic trials have not been performed.

Publications

• Type: Journal Articles Status: Published Year Published: 2018 Citation: Stafford EG, Tell LA, Lin Z, Davis J, Vickroy TW, Riviere JE, Baynes RE. (2018). FARAD Digest: Consequences of fipronil exposure in egg-laying hens. J. Am. Vet. Med. Assoc. 253(1):57-60, 2018. [PMID: 29911954]
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Mzyk D, Bublitz C, Hobgood G, Martinez M, Davis JL, Smith G, Baynes R. Effect of age on plasma protein binding of several veterinary drugs in dairy calves, Res Vet Sci, 121:59-64, 2018. [PMID: 30359812]
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Martin KL, Clapham MO, Davis JL, Baynes RE, Lin Z, Vickroy TW, Riviere JE, Tell LA. Extralabel drug use in small ruminants. J. Am. Vet. Med. Assoc 253(8):1001-1009, 2018. [PMID: 30272520]
• Type: Journal Articles Status: Awaiting Publication Year Published: 2019 Citation: Li M, Cheng YH, Chittenden JT, Baynes RE, Tell LA, Davis JL, Vickroy TW, Riviere JE, Lin Z. Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically-based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration. Arch Toxicol, in press, 2019. [PMID: 31025081]