farad-withdrawal

# FARAD Withdrawal ## Overview FARAD (Food Animal Residue Avoidance Databank) is the federally funded resource for drug withdrawal interval recommendations in food-producing animals. Maintained by UC Davis School of Veterinary Medicine, FARAD provides evidence-based guidance for both FDA-approved label withdrawals and extralabel drug use (ELDU) withdrawal determinations when commercial withdrawal data is unavailable. ## What is FARAD? **Definition:** Database and consultation service that provides withdrawal interval recommendations to ensure food animal products (meat, milk, eggs, honey, aquaculture) are safe for human consumption. **Regulatory Authority:** - Established under AMDUCA (Animal Medicinal Drug Use Clarification Act) - Endorsed by FDA CVM, USDA-APHIS, state veterinary boards - Primary resource for veterinarians determining ELDU withdrawal times - Non-regulatory (advisory); veterinarian makes final determination **What FARAD Provides:** - Withdrawal time recommendations (in days for meat, hours for milk, days for eggs) - Pharmacokinetic basis and safety margins - Relevant literature citations - Species-specific calculations - Conservative ("extra-safe") vs. standard margin options - Written recommendation documentation for veterinary records ## Contact Information **Phone Consultation:** - **Primary Line:** 1-888-873-2723 (1-888-USFARAD) - **Hours:** Monday-Friday, 8:00 AM - 4:30 PM Pacific Time - **Wait Time:** Typically 24-48 hours for response (urgent cases prioritized) **Email Submission:** - **Email:** FARAD@ucdavis.edu - **Turnaround:** 2-3 business days for written response **Online Database:** - **Website:** https://www.farad.org - **Search Field:** Can query commonly used drugs with pre-calculated withdrawals (convenience lookup) - **Not All Drugs:** Limited to most frequently used compounds; custom consultations needed for novel drugs **Fax (legacy):** - Available for formal submission; phone/email preferred ## Species Covered by FARAD **Primary (Most Comprehensive Data):** - Beef cattle - Dairy cattle - Swine - Poultry (chickens, turkeys) - Sheep - Goats **Secondary (Limited Data Available):** - Horses - Aquaculture (farmed fish: salmon, catfish, trout) - Rabbits - Fur-bearing animals (minks) **Not Covered:** - Wildlife (deer, elk, wild boar - typically no withdrawal recommendations provided) - Companion animals (dogs, cats) - not food-producing; different regulatory framework ## When to Consult FARAD **Mandatory FARAD Consultation:** 1. **Extralabel Drug Use (ELDU):** Drug is being used off-label (species, dose, route, or indication) and NO withdrawal time is on the FDA-approved label 2. **Compounded Drug:** Compounded formulation has no standard withdrawal data 3. **Novel Drug Combination:** Multiple drugs given concurrently; unknown interaction on withdrawal time 4. **Accidental Exposure:** Animal exposed to prohibited substance (e.g., avermectin to dairy cow); need emergency withdrawal guidance **Recommended FARAD Consultation:** - Aminoglycoside use in dairy (complex pharmacokinetics; kidney residue concentration) - First-use of unfamiliar drug in food animal - Pediatric/geriatric animals where metabolism differs from standard (very old cattle with renal disease, neonatal animals) - Suspected drug interaction affecting residue depletion **Not Necessary:** - FDA-approved label withdrawal time is specified (use label without consultation) - Companion animal drug use (dogs, cats, birds - non-food) - Human medication used off-label in non-food animals ## What FARAD Provides in Recommendation **Standard FARAD Written Recommendation Includes:** 1. **Header Information:** - Date of recommendation - Consulting veterinarian name and contact - Drug name (generic + brand) - Species (beef, dairy, swine, etc.) - Target animal weight/age (if relevant) 2. **Dose & Administration:** - Specified dose (mg/kg or total dose) - Route of administration (PO, IV, IM, intramammary, feed) - Frequency (once daily, twice daily, single injection, etc.) - Duration of treatment (days) 3. **Withdrawal Recommendations:** - **Meat Withdrawal:** Number of days between last dose and slaughter/harvest for human food - **Milk Withdrawal:** Number of hours between last dose and milk collection for human consumption - **Egg Withdrawal:** Number of days for egg withdrawal (poultry only) - **Tissue Specificity:** If organ meats have different withdrawal (e.g., liver vs. muscle) 4. **Safety Margin Designation:** - **Standard Margin:** Based on pharmacokinetic data with typical safety buffer (1.5-2x) - **Conservative/Extra-Safe Margin:** Higher safety buffer (2-5x) recommended for: - First-time use of drug - High-value animals - Immunocompromised animals - Renal/hepatic impairment 5. **Pharmacokinetic Basis:** - Summary of half-life, clearance rate, tissue distribution - How withdrawal time was calculated - Assumptions (normal kidney/liver function, standard species physiology) 6. **Literature Citations:** - Published pharmacokinetic studies - Previous FARAD consultations if relevant - Manufacturer data if available - Why certain literature was used vs. alternative studies 7. **Special Considerations:** - Drug interactions if other medications given concurrently - Age/weight effects if non-standard - Disease state effects (renal/hepatic impairment = longer withdrawal) - Regional/market considerations (some countries stricter than US) ## Regulatory Framework: AMDUCA & Withdrawal **AMDUCA Permits Extralabel Drug Use When:** - Veterinarian establishes valid VCPR (client-patient relationship) - Drug is FDA-approved (for any species or indication) - No FDA-approved alternative exists or is unsuitable - Veterinarian determines safe withdrawal interval - Extra-label use is documented in medical record **Veterinarian Responsibility:** - Final determination of withdrawal time belongs to prescribing veterinarian (not FARAD, not pharmacist) - FARAD provides evidence-based recommendation; veterinarian may choose more conservative interval if justified - Withdrawal time must be documented in animal medical record and communicated to client - Veterinarian liable if withdrawal time is violated (residue in food = public health violation) **Client Responsibility:** - Client (producer) must adhere to withdrawal interval - Cannot slaughter/milk/egg collect until withdrawal has elapsed - Client must track withdrawal dates (typically calendar notation, tags on animal pens) - Violation results in carcass/product condemnation and potential legal action ## Common Extralabel Drug Withdrawal Examples | Drug | Species | Indication | Label Status | FARAD Recommendation | |------|---------|-----------|------------------|---------------------| | Doxycycline IV | Cattle | Pneumonia | Oral approved only | 3-5 days meat (conservative) | | Sildenafil | Horse | Pulmonary hypertension | No approval | 5-7 days (experimental; consult for specific case) | | Albuterol IV | Swine | Respiratory | Feed-based approved | 1-2 days (IV is extra-label) | | Tramadol | Poultry | Pain | No approval | 5-7 days eggs (contact FARAD; rarely available) | | Acyclovir | Cattle | Viral infection | No approval | May not be available (novel antiviral) | ## How to Submit a FARAD Request **Telephone Request (Fastest for Emergency):** 1. Call 1-888-873-2723 2. Describe animal, disease, drug name/dose/route/frequency 3. Provide species, approximate weight, health status 4. FARAD consultant provides verbal recommendation immediately or within 24 hours 5. Document in medical record **Email/Online Submission:** 1. Go to https://www.farad.org 2. Click "Submit a Consultation" 3. Complete form: - Your contact information - Consulting veterinarian name/license # - Animal species, weight, age, health status - Drug name (generic + brand), dose, route, frequency, duration - Indication (disease/condition being treated) - Reason for extralabel use (label not available, unsuitable dose, etc.) - Any concurrent medications 4. Submit; FARAD responds via email in 2-3 business days **Written Documentation Requirements:** - VCPR established (client-patient relationship documented) - Clear justification for extralabel use - Specific drug + dose + route + frequency + duration - Target withdrawal product (meat, milk, egg) - Any comorbidities affecting metabolism ## Using FARAD Online Database Search **Searchable Field (Limited Database):** - Drug name (generic or brand): "doxycycline", "amoxicillin", "flunixin" - Species: "beef cattle", "dairy cattle", "swine", "poultry" - Pre-calculated withdrawal times for most-used compounds - NOT a complete database; novel drugs/combinations require consultation **Search Steps:** 1. Go to https://www.farad.org 2. Navigate to "Database Search" 3. Enter drug name + species 4. View pre-calculated withdrawal times if available 5. If not found: submit custom consultation ## Safety Margin Interpretation **Standard Safety Margin (1.5-2x):** - Withdrawal time = (mean time to residue <tolerance) × 1.5-2 - Suitable for: standard animals, normal renal/liver function, single drug use - Risk: if pharmacokinetics slightly slower than assumed, residue may remain above tolerance **Conservative/Extra-Safe Margin (2-5x):** - Withdrawal time = (mean time to residue <tolerance) × 2-5 - Suitable for: first-use, high-value animals, immunocompromised, renal/hepatic impairment, critical food safety - Lower risk of residue violation; longer withdrawal period requires client compliance planning **Example:** Drug X residue depletes below tolerance in 10 days in healthy animal. - Standard margin recommendation: 15 days - Conservative margin recommendation: 20-25 days - Veterinarian may choose either based on clinical judgment and client compliance capability ## Limitations of FARAD Recommendations - **Pharmacokinetic Assumptions:** Based on normal animal; disease (renal failure, hepatic disease) alters clearance (veterinarian may extend withdrawal) - **Tissue Distribution Variation:** Some drugs concentrate in specific tissues (kidney, liver); standard calculations may not account for organ-specific withdrawal - **Novel Drug Combinations:** FARAD may lack data; may recommend extra-conservative margin or defer to veterinary literature - **Regional Variation:** Some countries have different tolerances; FARAD primarily addresses US FDA tolerances - **Limited Data for Exotic Species:** Horses, aquaculture, rabbits have fewer pharmacokinetic studies; may recommend longer withdrawal or suggest literature review - **Client Compliance:** FARAD recommendation is only as good as producer adherence; veterinarian must verify tracking and enforcement ## Integration with Veterinary Practice **Workflow:** 1. Treat food animal off-label 2. Call FARAD immediately or within 24 hours 3. Document FARAD recommendation in medical record with date/time of consultation 4. Communicate withdrawal end date to client in writing (calendar, tag on animal pen) 5. Verify at slaughter/milk pickup that withdrawal has elapsed 6. Document final product disposition (sold, held, destroyed if violated) **Medical Record Documentation:** ``` Date: 2024-03-18 Animal: Dairy cow #42, Holstein, 500 kg Diagnosis: Clinical mastitis Treatment: Ceftiofur IV 1 g daily × 3 days (ELDU - no label approval for IV) FARAD Consultation: 888-873-2723, consulted 3/18/2024 FARAD Recommendation: 7 days meat withdrawal, 24 hours milk withdrawal (standard margin) Withdrawal End Date: 3/25/2024 for meat; 3/19/2024 for milk Client Notified: Yes, verbally + written instruction sheet ``` ## Sources - **FARAD Website:** https://www.farad.org - **FARAD Phone:** 1-888-873-2723 - **AMDUCA Guidance (FDA CVM):** https://www.fda.gov/animal-veterinary/guidance-documents - **UC Davis School of Veterinary Medicine:** Hosts FARAD - **Plumb's Veterinary Drug Handbook (current edition):** Withdrawal time tables - **Approved Animal Drug Products (Green Book):** Official label withdrawal times