Withdrawal Times

Overview

Withdrawal times (WDI: withdrawal interval) are the mandatory waiting periods between last drug administration and harvest/food product collection in food-producing animals. Violating withdrawal times results in drug residues in food, violating FDA tolerances and food safety regulations. This skill covers withdrawal time concepts, sources, common examples, and extralabel use (ELDU) considerations.

When to Use

• User asks about safe-to-slaughter or safe-to-milk/egg intervals after drug treatment
• User treats a food animal and needs withdrawal time for any administered drug
• User asks about FARAD recommendations for extralabel drug use
• User questions whether a residue is safe for human consumption
• Keywords: withdrawal, WDI, residue, FARAD, MRL, tolerance, meat, milk, egg, slaughter, food safety, ELDU

What Are Withdrawal Times?

Definition: Minimum time between last drug dose and when treated animal may be slaughtered for meat, milked for human consumption, or eggs collected for human use.

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