Most people who come to me from the animal health side have the same first question: which GMP regulation actually applies to us? The answer depends on what you make, and it is less obvious than it sounds. A company producing a Type A medicated article is under a different part of Title 21 than the feed mill that turns that article into a Type C feed, and both differ from the company filling injectable vials for dogs. Get that wrong and you spend months building a quality system around the wrong rulebook.
This guide walks through how 21 CFR Part 225 (medicated feeds) and 21 CFR Part 226 (Type A medicated articles) work, where 21 CFR Parts 210 and 211 still come into play, and what I think matters most when FDA's Center for Veterinary Medicine (CVM) and field investigators look at your operation.
Which GMP Regulation Applies to Veterinary Drugs?
Three sets of regulations cover most of the veterinary drug manufacturing world, with 21 CFR 558.6 layered on top for VFD feed. Which one governs you depends on the product form.
- 21 CFR Part 226 covers Type A medicated articles, the concentrated drug-plus-carrier products that are the starting point for medicated feeds.
- 21 CFR Part 225 covers medicated feeds, meaning Type B and Type C feeds made from Type A articles, including feeds that contain veterinary feed directive (VFD) drugs.
- 21 CFR Parts 210 and 211 cover finished pharmaceuticals. Section 211.1(a) states that Part 211 sets minimum current good manufacturing practice for drug products intended for administration to humans or animals, so a veterinary tablet, injectable, topical, or oral liquid sits under Part 211 just as a human drug does.
The definitions of Type A, Type B, and Type C sit in 21 CFR 558.3(b). In plain terms, a Type A medicated article is the concentrated product made by a drug manufacturer, a Type B feed is an intermediate that is further diluted, and a Type C feed is the complete feed or top-dress that the animal actually eats. Part 558 also lists, drug by drug, the approved uses, limitations, and permitted combinations, which means it is the document your formulation has to agree with before any GMP question even comes up.
| Product | Primary GMP regulation | Typical manufacturer | Core concern |
|---|---|---|---|
| Veterinary tablets, injectables, topicals, liquids | 21 CFR Parts 210 and 211 | Animal health pharmaceutical company, contract manufacturer | Full finished-pharmaceutical quality system |
| Type A medicated article | 21 CFR Part 226 | Drug sponsor or contract manufacturer making premixes | Potency, uniformity, labeling, records |
| Type B and Type C medicated feed | 21 CFR Part 225 | Feed mill, integrator, on-farm mixer | Carryover, cross-contamination, assay, distribution records |
| Feed containing a VFD drug | Part 225 plus 21 CFR 558.6 | Feed mill and distributor | CGMP plus VFD recordkeeping |
If you make more than one of these, you are managing more than one regime under one roof. That is common in animal health, and it is where most of the confusion starts.
Medicated feed mills have one more boundary to manage: 21 CFR Part 507, the FSMA animal food CGMP and preventive controls rule. Part 507 applies to animal food facilities generally, while Parts 225 and 226 are the drug-specific CGMP for medicated feed and Type A articles. A mill making medicated feed should not assume one replaces the other. Check how Part 507, including the exemptions in 507.5, applies to your facility, and keep the two programs consistent rather than running parallel systems.
What Does 21 CFR Part 225 Require of Medicated Feed Manufacturers?
Section 225.1 sets the legal consequence plainly: a medicated feed that is not manufactured in conformity with the part is adulterated under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. That is the hook FDA uses. A deficiency in Part 225 is not a paperwork problem. It makes the product itself legally adulterated.
The part is shorter than Part 211, but it asks for the same habits: written procedures, trained people, controlled materials, and records that let you reconstruct what happened. The sections I find myself walking clients through most often are these.
Personnel, buildings, and equipment (225.10, 225.20, 225.30)
Section 225.10 expects that the people handling medicated feed have the training and experience for the job, and that someone in management is responsible for the program. Sections 225.20 and 225.30 address buildings and equipment: they should be suitable in size, design, and construction for the operation, kept clean, and maintained so that they do not introduce contamination. Scales and metering devices need to be accurate for the drug being weighed. A premix that goes into a ton of feed at a few grams per ton makes a small weighing error a big dosing error.
Using shared areas and equipment (225.35)
Section 225.35 deals with work areas, equipment, and storage areas that are also used for other manufacturing or storage purposes. Almost every feed mill is a shared facility, because a mill rarely makes only medicated feed. This section is where your cross-contamination control story starts, and in my experience it is the section inspectors lean on when the facility has no dedicated lines.
Components (225.42)
Section 225.42 covers drug components and other ingredients: how they are received, identified, stored, and used. Medicated articles need to be traceable to the lot, held under conditions that protect them, and used within their labeled limits. For a VFD drug, I also recommend building a check into receiving that confirms you are authorized to hold and use it. That is good practice rather than text in 225.42; the VFD obligations themselves sit in 21 CFR 558.6.
Laboratory controls and assay (225.58)
Section 225.58 requires laboratory controls that verify the medicated feed contains the drug at the intended level. For a mill, that usually means a program of periodic assays of finished Type B and Type C feeds, . Beyond what the section requires, I recommend a documented method for deciding what to do when a result is out of range. I would encourage clients to think of the assay program as their only direct evidence that mixing is working. Everything else is inference.
Equipment cleanout and drug carryover (225.65)
If I had to pick one section that causes the most trouble, it would be 225.65. It requires adequate procedures, established and followed, to prevent unsafe contamination of medicated feed by drug carryover from the previous batch. In practice that means a defined approach to flushing, sequencing, or physical cleanout, with a rationale for why the chosen method is enough for the drug in question. A sequence plan that runs the highest-risk drug before a sensitive species feed, with nothing between, is the kind of thing that ends up on a Form FDA 483.
Labeling (225.80)
Section 225.80 covers labeling controls: the labels need to match the approved use, they need to be reconciled, and the wrong label must not reach the wrong feed. Labeling mix-ups are a recurring recall cause across the FDA-regulated world, and animal feed is no exception.
Master record file, production records, distribution, and complaints (225.102, 225.110, 225.115)
Section 225.102 requires a master record file and production records for each batch. Section 225.110 requires distribution records so you can trace where each batch went, and 225.115 requires a complaint file. Each of those sections sets its own retention period, and Part 226 has parallel requirements in 226.102, 226.110, and 226.115. Confirm the exact periods against the current eCFR before you write a records procedure, rather than relying on anyone's summary, including mine.
What Does 21 CFR Part 226 Require for Type A Medicated Articles?
Part 226 follows a similar outline to Part 225, with the same sequence of sections: general provisions in 226.1, personnel in 226.10, buildings and facilities in 226.20, equipment in 226.30, then production and process controls in 226.40, components in 226.42, laboratory controls in 226.58, packaging and labeling in 226.80, and records in 226.102, 226.110, and 226.115.
The difference is in the stakes. A Type A article is the most concentrated form of the drug in the whole supply chain, so an error made at this stage is multiplied by every downstream dilution. A few points that I think deserve emphasis for Part 226 manufacturers:
- Potency and uniformity are the product. A Type A article that is not uniform cannot be fixed by the feed mill later. Your mixing validation and your in-process and release testing carry more weight here than anywhere else in the animal feed chain.
- Packaging and labeling control (226.80) is tight for a reason. The label tells the downstream user the drug, the concentration, and the permitted use. A mislabeled Type A article can contaminate a large volume of feed before anyone notices.
- Lot-level distribution records (226.110) are what make a recall possible. If you cannot say which feed mills received which lots, a recall becomes a broad one.
- Complaints (226.115) travel upstream. Feed mills that find a drug level out of range will often call the Type A supplier first, and what you do with that call is exactly what an investigator will ask to see.
Part 226 is sometimes treated as a lighter version of Part 211. It is a different tool, built for a product that is itself an intermediate. Part 226 has no formal quality-unit requirement like 211.22, but it expects equivalent accountability for approving materials, processes, and records.
Where Does Part 211 Still Apply to Veterinary Drugs?
If your product is a finished dosage form such as a tablet, injectable, or topical, you are in Part 211 territory, and the expectations are the same as for human drugs: a quality control unit with authority (211.22), written production and process controls (211.100), laboratory controls (211.160), stability testing (211.166), and complete batch records (211.188). Sterile veterinary products carry the additional aseptic processing expectations that apply to any sterile drug, and FDA's aseptic processing guidance applies in spirit even though it was written primarily with human products in mind.
Two practical points come up repeatedly.
First, a company that makes both a veterinary premix and a veterinary injectable needs to be clear in its quality manual which part governs which line. I have seen quality systems written entirely to Part 211 and then applied to a medicated feed operation without ever referencing Part 225, which leaves out the carryover and assay requirements that an investigator will look for first. The reverse also happens.
Second, stability matters for veterinary products as much as for human ones. The expiry date on a Type A article or a veterinary injectable needs a data-backed basis, and I covered the fundamentals in our guide to stability testing.
How Does the Veterinary Feed Directive Change GMP Obligations?
The VFD framework in 21 CFR 558.6 governs medically important antimicrobials in feed. It is a separate set of requirements from Part 225, but a mill that handles a VFD drug has to satisfy both. Part 225 asks whether the feed was made correctly. Section 558.6 asks whether you were allowed to make and distribute it, which depends on a valid VFD from a licensed veterinarian, the right acknowledgment from the distributor, and the required records.
FDA's Guidance for Industry #213 set the path for moving medically important antimicrobials in feed under veterinary oversight, and the agency later issued Guidance for Industry #263 to bring the remaining products still available over the counter under the same prescription framework. GFI #213 was finalized in December 2013, the VFD final rule followed in 2015, and the VFD requirements took full effect on January 1, 2017. GFI #263 moved the remaining over-the-counter products to prescription status, with the transition completed on June 11, 2023. The practical effect is that mills that once handled only non-medicated rations may now handle VFD feed. If your mill is one of them, your training program and your records need to reflect that.
What Do FDA Investigators Look at in a Medicated Feed Inspection?
FDA's field inspections of feed manufacturers are guided by Compliance Program 7371.004, which covers feed manufacturing. The program gives investigators a roadmap that tracks closely with Part 225 and Part 226, and it is worth reading before you are inspected rather than after. My experience is that the findings cluster in a few places.
| Area | What investigators tend to ask | Weakness I commonly see |
|---|---|---|
| Carryover control (225.65) | What is your cleanout or flush method, and what data supports it? | Procedure exists but the rationale does not |
| Assay program (225.58) | How often do you assay, and what happens when a result fails? | Assays done, but out-of-range results not investigated |
| Shared equipment (225.35) | How do you prevent cross-contamination between medicated and non-medicated feed? | Sequencing relied on informally |
| Labeling (225.80) | How do you reconcile labels and prevent mix-ups? | No reconciliation record |
| Records (225.102, 225.110) | Can you trace this batch from components to customer? | Incomplete batch records, missing distribution detail |
| Complaints (225.115) | Show me your complaint file. | No file, or no evidence of follow-up |
The thread running through that table is that investigators are not mostly looking for exotic failures. They are looking for the procedure that exists on paper and has no evidence behind it. In my view, that is the single most useful thing to remember when you prepare. Our FDA inspection preparation page lays out how I approach a mock inspection for that reason.
How Do You Build a Compliant Quality System for a Veterinary Drug Operation?
I tend to recommend a sequence rather than a checklist, because the order in which you fix things matters.
Step 1: Decide which regulations apply to which product
Make a simple inventory of every product, mark it as Type A, Type B, Type C, VFD feed, or finished dosage form, and map each to Part 226, Part 225, 558.6, or Part 211. This is a one-page document, and nearly every later decision depends on it.
Step 2: Assign quality responsibility clearly
Name the person who has authority to approve and reject. In a small mill this may be the plant manager wearing two hats, and that is acceptable as long as the responsibility is written down and the person has the training and standing to say no to a shipment.
Step 3: Write the carryover and cross-contamination plan first
Because carryover and shared-equipment controls (225.65 and 225.35) are where I most often see weak evidence, I would start there. Define your drug-by-drug risk, choose flushing, sequencing, or physical cleanout for each, and decide what evidence you will collect to show it works. Then collect it.
Step 4: Put the assay program on a schedule
Decide which products you will assay, how often, by which lab and method, and what action follows an out-of-range result. The part that gets skipped most often is the last one.
Step 5: Get records to the point where one batch can be reconstructed in an hour
Pick a batch at random and try to trace it from component receipt through mixing, assay, labeling, and shipment. If that takes days or turns up gaps, you have found the gap an investigator would find.
Step 6: Train and retrain
Section 225.10 and its Part 226 counterpart expect trained people, and training records are one of the first things asked for. See our overview of personnel training for how to structure it so it holds up under questioning.
Common Gaps I See in Veterinary Drug and Medicated Feed Operations
- Treating Part 225 as a feed-quality regulation only. It is a drug regulation applied to feed, and the adulteration language in 225.1 reflects that.
- A cleanout procedure with no verification. If you have never tested the first non-medicated batch after a medicated one, you do not know whether your procedure works.
- Mixing validation done once and never revisited. Equipment wears, ribbons loosen, and formulas change.
- Weak supplier control for Type A articles. The Type A supplier is your most important vendor, and a certificate of analysis you have never verified is a leap of faith.
- Complaint handling that stops at the phone call. A complaint file should show an investigation, a conclusion, and a decision about whether other batches are affected.
None of these is hard to fix. They tend to persist because everyone is busy making product and the procedures were written once and filed.
What Should You Do Next?
If you operate a Part 225 or Part 226 facility, or a combined veterinary drug site, the most useful first move is a gap assessment against the actual text of the regulations, followed by a mock inspection built on Compliance Program 7371.004. If you are standing up a new operation, how to become GMP compliant gives the broader sequence, and Part 225 and 226 specifics can be layered onto it. I would welcome the chance to talk through your situation. Where does your current quality system have the least evidence behind it?
Jared Clark, JD, MBA, PMP, CMQ-OE, CQA, CPGP, is a GMP Compliance Consultant at Certify Consulting (https://certify.consulting).
Frequently Asked Questions
What is the difference between 21 CFR Part 225 and Part 226?
Part 226 sets current good manufacturing practice for Type A medicated articles, the concentrated drug products used to make medicated feeds. Part 225 sets current good manufacturing practice for medicated feeds themselves, meaning Type B and Type C feeds. A company can be subject to one or both, depending on whether it makes the article, the feed, or both.
Does 21 CFR Part 211 apply to veterinary drugs?
Yes. Section 211.1(a) states that Part 211 contains minimum current good manufacturing practice for drug products intended for administration to humans or animals. Finished veterinary dosage forms such as tablets, injectables, and topicals fall under Part 211, while Type A medicated articles and medicated feeds fall under Parts 226 and 225.
What happens if a medicated feed is not made in compliance with Part 225?
Under section 225.1, a medicated feed not manufactured in conformity with Part 225 is considered adulterated under section 501(a)(2)(B) of the FD&C Act. That gives FDA grounds for enforcement actions including seizure, injunction, and recall requests, on top of inspectional observations.
Do I need a VFD to make feed containing an antimicrobial?
If the drug is a VFD drug, the feed can be distributed only under a valid veterinary feed directive, and the requirements for distributors and recordkeeping are in 21 CFR 558.6. That obligation is in addition to your Part 225 requirements.
What is the most common cause of FDA observations at medicated feed mills?
I have no FDA ranking to cite, but in my experience it is carryover and cross-contamination controls (225.65 and 225.35). See the inspection table above for the other recurring weaknesses.
Last updated: 2026-10-30
Jared Clark
GMP Compliance Consultant, Certify Consulting
Jared Clark is a GMP compliance consultant and founder of Certify Consulting, specializing in FDA GMP requirements for pharmaceuticals, dietary supplements, cosmetics, and food manufacturing.