21 CFR Part 225 – Medicated Feed cGMP Requirements

This topic is part of the SG Systems Global regulatory & operations glossary.

Updated October 2025 • Animal Food cGMP • Drug-in-Feed Controls & Records

21 CFR Part 225 establishes current good manufacturing practice (cGMP) requirements for facilities that manufacture, blend, or distribute medicated feeds—complete feeds, supplements, or premixes that contain approved new animal drugs. The rule’s aim is simple but unforgiving: ensure the right drug, at the right concentration, is consistently delivered to the right animals, without cross-contaminating other products or misbranding lots. That means documented control over incoming Type A medicated articles, controlled batching and mixing, validated cleanout/flush or sequencing to prevent carryover, correct labeling and distribution controls, periodic assays to verify potency, and records that make each medicated lot defensible from weighing through shipment. Part 225 sits alongside broader animal food expectations under 21 CFR 507 (FSMA animal food), drug conditions of use under 21 CFR 558, and data integrity expectations under 21 CFR Part 11 when records are electronic.

Practically, compliance with Part 225 means medicated feed mills operate like regulated drug-packaging lines: masters are controlled, scales and mixers are qualified and calibrated, operators follow signed instructions, materials are reconciled, and label versions match the approved claims and limitations. Because animals cannot self-advocate, dose mistakes show up as residues, therapeutic failures, or harm. Regulators therefore expect control to be engineered into the process—barcode checks at weigh, device-captured mix times and rpm, positive lot identification, and a paper or electronic trail that would withstand a recall or residue investigation. A mill might produce non-medicated and medicated feeds on the same equipment; Part 225 requires documented segregation, sequencing, or physical cleanout with evidence that carryover cannot exceed established limits.

“In medicated feed, ‘close enough’ is not compliant—dose error and carryover are defects you can’t see until it’s too late. Part 225 forces precision, proof, and accountability at every handoff.”

1) What It Is

21 CFR Part 225 codifies the minimum practices medicated feed mills must follow to consistently manufacture feeds with drugs at labeled concentrations and under approved conditions of use. It covers personnel qualifications, building and equipment design, component control (including Type A medicated articles and premixes), production and process controls, laboratory controls and assays, labeling and distribution procedures, and complaint/recall handling. The regulation distinguishes between mills manufacturing from approved/licensed Type A articles and those operating under a medicated feed license when required by a drug’s approval. Regardless of license status, mills must maintain master manufacturing formulas (MMFs), batch production records, and evidence of equipment calibration and cleaning sufficient to reconstruct, verify, and defend each lot’s conformance.

2) Scope & Key Intersections

Part 225 applies to facilities that manufacture medicated feeds for commercial distribution or for use in their own herds when produced for sale. It intersects with: (a) Part 507 (animal food cGMPs and hazard analysis/PC) for broader sanitation, pest control, and preventive controls; (b) 21 CFR 558 for drug listings, approved concentrations, and veterinary feed directive (VFD) conditions of use; (c) 21 CFR 501 for animal food labeling; and (d) Part 11 if records are electronic. Device and pharma concepts—Document Control, ALCOA+, Audit Trail—are increasingly expected in modern mills.

3) Core Requirements & Controls

Personnel & training. Qualified individuals must understand drug handling, weighing/dispensing, mixing, labeling, and sanitation procedures. Training is documented and tied to current versions of SOPs and MMFs under Document Control.

Buildings & equipment. Facilities prevent mix-ups and cross-contamination: dedicated/segregated storage for Type A articles, weather/dust control, labeled bins, and equipment of suitable size and capability. Mixers and scales are identified, calibrated on schedule, and maintained with calibration status visible.

Components & drug control. Type A articles and premixes are received from approved suppliers, identified with lot numbers, stored to prevent deterioration, and reconciled. Positive identification and status control (Component Release) ensure only approved drugs at the correct potency enter batching.

Master formulas & batch records. Each medicated product has an MMF (formula, theoretical yield, drug concentration, sequence, mixing parameters) and a batch record capturing lot numbers, actual weights, equipment used, mixing time/speed, flush/sequencing steps, operator/QA signatures, label ID, and yield reconciliation.

Production controls. Gravimetric or volumetric weighing with verification, barcode checks, device-captured mix times, and interlocks to prevent proceeding without required scans/signatures. Sequencing/flush/physical cleanout are specified and documented to prevent carryover into subsequent non-medicated or lower-dose feeds.

Label control & distribution. Labels reflect the approved claims, concentrations, species, limitations, withdrawal times, and lot/expiry. Issuance and reconciliation prevent wrong-label application. Distribution records identify consignee, product, lot, and quantity to enable rapid trace/recall.

Laboratory controls. Periodic potency assays verify drug concentration at label claim within tolerance; suspect or out-of-range results trigger containment, investigation, and corrective action.

Complaints & recalls. Mills maintain complaint files, investigate medically significant events, and execute mock recalls to verify retrieval speed and completeness.

4) Drug Handling, Carryover & Cleanout

Carryover is the signature risk of medicated feed. Controls include: physical segregation of drug storage; dedicated or clearly identified dosing equipment; documented sequencing (e.g., high to low potency, medicated to non-medicated with flush lots in between); validated flush quantities and materials; physical cleanout/inspection criteria; and swab or targeted assay checks after maintenance. Where continuous blending or shared conveyors exist, risk assessments justify the cleanout strategy and limits for residual drug. Records must show exactly which lot followed which, the flush used, and where the flush was routed (sold as such, reworked, or discarded) to prevent inadvertent dosing of uninvolved animals.

5) Calibration, Mix Uniformity & Assays

Right dose requires two things: accurate weighing and uniform mixing. Scales, loss-in-weight feeders, and flow meters are calibrated against traceable standards; status is displayed and interlocked. Mixers are qualified to achieve homogeneity at the specified load, time, and rpm; representative sampling demonstrates coefficient of variation (CV) below internal limits for both tracer and drug assays. Periodic drug assays (in-process or finished feed) confirm label claim within allowed tolerances; failures trigger deviation, containment of affected distribution, root cause, and retest. Trends are reviewed for drift, with preventive maintenance or process adjustment when CV or assay centering worsens.

6) Labeling & Claims Governance

Labels are not marketing; they are legal instructions and claims tied to approvals. Masters specify exact wording, drug concentration, intended species and class, directions, limitations (including VFD conditions when applicable), withdrawal times, lot/expiry format, and GTIN/barcode where used. Issuance is controlled under Labeling Control; printing at point-of-pack requires version checks and reconciliation of issued/applied counts. Any change to label content routes through Change Control with regulatory review as needed.

7) Data Integrity & Electronic Records

Whether paper or electronic, batch documentation must be complete, contemporaneous, and attributable. Electronic Batch Records (eBMR) should enforce unique user IDs, time-stamped entries, device integrations for scales/mixers, and immutable audit trails. Calculations (e.g., theoretical vs. actual drug inclusion) are system-calculated to reduce transcription errors. Attachments—assay results, photos of cleanout—are linked to the lot. Systems that meet Part 11 expectations are far more defensible during investigations or residue inquiries.

8) Common Failure Modes (and How to Avoid Them)

Wrong drug or concentration weighed. Countermeasure: barcode-directed weighing, dual verification for drug additions, scale interlocks, and Dual Verification on critical steps.

Carryover into non-medicated feed. Countermeasure: validated sequencing/flush plans, physical cleanout with inspection, and periodic residue assays on first-off post-flush lots.

Out-of-tolerance assays. Countermeasure: re-qualify mixer load/time; verify drug premix potency; retrain on weighing technique; increase in-process sampling.

Mislabeled lots. Countermeasure: label issuance control, print-at-pack with template lock, reconciliation and scan-before-ship.

Incomplete records. Countermeasure: eBMR with enforced fields, device-captured times/weights, required reason codes for overrides, and supervisor reviews before release.

9) Metrics & Management Review

Assay pass rate and delta from label claim; CV of mix uniformity; percent lots requiring rework due to label or documentation errors; first-off residue checks post-flush; complaint rate related to efficacy or residues; recall/mock recall retrieval time; right-first-time batch record completion; calibration on-time % for scales and mixers. Management reviews trends at least quarterly and ties signals into CAPA and preventive maintenance planning.

10) How This Fits with V5

V5 by SG Systems Global operationalizes Part 225 requirements from gate to gate. In V5 WMS, Type A medicated articles are received with barcode validation, quarantined until Component Release, and stored in segregated bins with FEFO rotation. Directed dispensing uses scanner prompts, verified scales, and tolerance windows; over/under additions trigger holds. In V5 MES, the master manufacturing formula is controlled; batch steps enforce mixer ID, load %, time/rpm capture, and sequencing/flush prompts. Photo evidence of cleanout is required when changing from medicated to non-medicated SKUs. Labels are issued through Labeling Control with template locks and reconciliation; pallets cannot ship until scans match order/lot. Results, assays, and deviations flow to V5 QMS for trending and CAPA. All records carry audit trails and Part 11 e-signatures, giving QA defensible evidence at lot release and during regulatory inspections.

11) Practical Walkthrough (Example)

A regional mill produces a swine grower feed medicated with a Type A article at 100 g/ton. V5 WMS receives the drug, scans GTIN/lot, and quarantines it pending CoA verification. QA performs identity testing on the first receipt from a new supplier and releases the lot. Production schedules a batch; V5 MES pulls the MMF and enforces dispensing by barcode and scale tolerance. The operator attempts to weigh the wrong drug lot; the scan blocks the step. After correct dispense, the system verifies mixer ID and auto-captures mix time/rpm from the HMI. Because the previous run was non-medicated poultry feed, the eBMR requires a validated flush sequence; the operator selects the defined flush material, runs it, photographs the cleanout, and records the flush lot destination. Labels are printed from locked templates showing species, dose, limitations, and withdrawal; issuance and application are reconciled with scans. Samples are pulled for a potency assay; results meet label claim. Batch review-by-exception is clean, and the lot proceeds to shipment with full distribution traceability. A month later, a customer inquiry prompts a targeted record pull; QA renders the full batch package, including device data, in minutes.

12) FAQ

Q1. Do all medicated feed mills need a medicated feed license?
Not always. A license is required for certain drugs/uses specified in approvals; others can be produced without a license if Part 225 cGMPs are met. Check the drug’s listing and conditions of use.

Q2. How often must potency assays be performed?
Part 225 expects periodic assays sufficient to verify control. Frequency is risk-based—consider drug criticality, process capability, and history. Out-of-range results require investigation and containment.

Q3. Can sequencing/flush replace physical cleanout?
Yes, if validated. Mills must document that the sequence and flush quantity/material reduce carryover below defined limits, and keep records proving execution for each changeover.

Q4. What records are required for each batch?
At minimum: MMF reference, component lots and amounts, equipment IDs, mix parameters, cleanout/flush details, label template ID and reconciliation, yield, signatures, assay results when applicable, and distribution records.

Q5. How does Part 225 relate to FSMA’s Part 507?
Part 225 is drug-in-feed specific cGMP; Part 507 adds broader animal food cGMPs and preventive controls. Most mills must comply with both, coordinating sanitation, pest control, and hazard analysis with drug controls.

Related Reading
• Foundations & Records: Document Control | Data Integrity | Audit Trail (GxP) | 21 CFR Part 11
• Animal Food & Drug: 21 CFR Part 507 | Labeling Control | EPCIS Traceability
• Execution & QA: Electronic Batch Record (eBMR) | Gravimetric Weighing | CPV | CAPA