Withdrawal Times

Regulatory Basis:

• FDA CVM establishes tolerances for approved drugs (maximum residue limits = MRLs)
• Tolerance = safe residue level in tissue/milk/egg at zero ppm (no detectable) to X ppb (parts per billion)
• Label withdrawal time = manufacturer data to ensure residue drops below tolerance
• ELDU withdrawal time = veterinarian-determined safe interval for off-label use (more conservative)

Key Species and Products:

• Beef cattle: meat, milk (dairy), hide/offal
• Dairy cattle: milk, meat (cull animals), butter/cheese derivatives
• Swine: meat, organ meats, fat
• Poultry (chickens, turkeys): meat, eggs, organ meat
• Sheep/goats: meat, milk, wool/hide

Common Drug Withdrawal Examples

FARAD (Food Animal Residue Avoidance Databank)

What is FARAD? Federally funded database of withdrawal recommendations for FDA-approved and extralabel drugs in food animals. Managed by UC Davis; primary source for ELDU guidance.

When to Use FARAD:

• Drug is used off-label (species, dose, frequency, or indication not on label)
• Off-label use is permitted under AMDUCA but withdrawal time is NOT specified
• Veterinarian must determine safe withdrawal interval
• FARAD provides evidence-based recommendations

How to Contact:

• Phone: 1-888-873-2723 (1-888-USFARAD)
• Email: [email protected]
• Website: https://www.farad.org
• Provides written recommendations with reference citations
• Typically 2-3 business day turnaround

FARAD Recommendations Include:

• Target species and weight range
• Dose, route, frequency used
• Withdrawal time for meat (days to slaughter)
• Withdrawal time for milk (hours to next collection)
• Withdrawal time for eggs (days to next collection)
• Supporting pharmacokinetic references
• Safety margin notation (conservative vs. standard)

Extralabel Drug Use (ELDU) and Withdrawal

AMDUCA Permits ELDU When:

• FDA-approved drug exists but is unsuitable (wrong species, dose, formulation)
• Veterinarian establishes VCPR and prescribes the drug
• Veterinarian determines safe withdrawal interval
• Extra-label use is documented in medical record

ELDU Withdrawal Requirements:

• Veterinarian responsible for establishing withdrawal time (not manufacturer)
• Must be conservative; typically 2-10x longer than label withdrawal for similar approved products
• FARAD consultation is strongly recommended for food animals
• No withdrawals should be assumed to be safe; document veterinary reasoning
• Client informed that meat/milk/eggs may not be market-safe until withdrawal elapses

Example ELDU Scenario: A dairy farmer treats a cow with doxycycline (200 mg IV) off-label for atypical pneumonia. Doxycycline is approved for cattle but only oral/feed formulations; IV route is off-label. Veterinarian consults FARAD, which recommends 5-day meat withdrawal + 24-hour milk withdrawal (conservative vs. approved oral formulation). Milk is discarded 24 hours; meat is safe 5 days post-treatment.

Species-Specific Considerations

Cattle (Beef & Dairy):

• Milk withdrawal is critical; zero tolerance for many antimicrobials
• Fat-soluble drugs (macrolides, ionophores) have long withdrawals
• Renal impairment increases withdrawal times dramatically
• Separate meat and milk withdrawal calculations

Swine:

• Shorter withdrawal times than cattle (faster metabolism)
• Organ meats (liver, kidney) often have higher residue levels; verify handling
• Regulatory pressure to reduce antimicrobial use; consider non-drug alternatives

Poultry:

• Eggs have unique withdrawal; cannot pool eggs until withdrawal lapses
• Spent laying hens may still be in withdrawal; label clearly
• Broilers: typically 3-7 day withdrawals (shorter lifespan)
• Turkeys: verify species-specific data; labeled for chickens ≠ turkeys

Sheep/Goats (Milk & Meat):

• Fewer approved drugs; ELDU common
• Milk withdrawal for dairy goats critical (similar to dairy cattle)
• Meat withdrawal often longer due to fat distribution

Workflow: Determining Withdrawal Safety

1. Identify Drug & Route: Specific product, dose, route (PO, IM, IV, intramammary)
2. Check Label: Does labeled indication match clinical use and species?
3. If On-Label: Use label withdrawal time; no veterinary calculation needed
4. If Off-Label (ELDU):
   • Verify AMDUCA-permitted (approved drug, legitimate medical reason, VCPR)
   • Consult FARAD or pharmacokinetic literature (Plumb's Handbook)
   • Establish conservative withdrawal interval (document reasoning)
   • Record withdrawal time in medical record
5. Client Communication: Specify withdrawal date/time in writing; mark animal/pen clearly; track with calendar/management software
6. Compliance Verification: At slaughter/milk pickup/egg collection, confirm withdrawal has elapsed before food product enters commerce

Tolerance/MRL Basis

FDA CVM establishes tolerances based on:

• Animal toxicology studies
• Human food safety assessment (Acceptable Daily Intake = ADI)
• Pharmacokinetic data (residue depletion rate)
• Manufacturing consistency

Tolerances are published in 21 CFR 556. Zero tolerance (undetectable) is common for antimicrobials.

Sources

• FARAD Database: https://www.farad.org (primary resource for ELDU)
• FDA CVM Tolerances (21 CFR 556): https://www.fda.gov/animal-veterinary/cvm-updates
• Plumb's Veterinary Drug Handbook (current edition): withdrawal sections
• Approved Animal Drug Products (Green Book): includes withdrawal times
• AMDUCA Guidance (FDA CVM): extralabel use regulations
• Food Animal Residue Avoidance Databank refereed publications (Animal Drugs)

Limitations

• Withdrawal times are conservative estimates; individual variation exists (age, health, liver function)
• This skill provides reference information; clinical decisions require veterinary judgment
• Regional regulations vary (US FDA vs. EU, Canada, Australia have different tolerances)
• Novel drugs or unusual combinations may lack published withdrawal data; FARAD consultation mandatory
• Client compliance (actually waiting the withdrawal period) is veterinarian's responsibility to verify