FDA's GFI #256B: Compounding Animal Drugs Under CGMP

On 28 August 2026, the US Food and Drug Administration published a new draft guidance for the animal-health industry. Guidance for Industry #256B, titled Compounding Animal Drugs from Bulk Drug Substances: Compounding under CGMP in Federally-Registered Facilities, proposes to extend the agency's enforcement approach to a new type of compounder. The document is short, but its direction is significant. For the first time, FDA is describing when it will not take action against animal drugs compounded from bulk substances at facilities that are registered with FDA and operate under current good manufacturing practice, or CGMP. Comments are open until 27 November 2026.

For most Canadian regulatory and quality leaders, animal-drug compounding sits at the edge of the radar. It should not. Contract manufacturers, outsourcing facilities and conventional drug makers that serve, or want to serve, the US veterinary market are exactly the audience GFI #256B addresses. The guidance also signals a broader theme that carries across borders and species: regulators increasingly want unapproved and compounded products made under the same quality discipline as approved ones. This article explains what GFI #256B says, how it fits with the existing final guidance GFI #256, and what it means for firms weighing an FDA registration or a US veterinary line.

Executive summary

GFI #256B builds on FDA's final guidance GFI #256, which the agency announced in the Federal Register of 14 April 2022. GFI #256 set out when FDA does not intend to take enforcement action against veterinarians and pharmacists who compound certain animal drugs from bulk drug substances in state-licensed pharmacies or federal facilities. GFI #256B adds a third category, federally-registered facilities, meaning facilities registered with FDA as outsourcing facilities under section 503B(b) or as drug establishments under section 510(b) of the Federal Food, Drug, and Cosmetic Act. The trade-off FDA is testing is quality for flexibility: products made under CGMP carry fewer quality concerns than those compounded outside CGMP, so the agency is exploring whether a CGMP-based policy should reach more products. FDA plans to fold GFI #256B into the final GFI #256 once comments are considered.

• GFI #256B is a draft guidance published 28 August 2026, with comments open until 27 November 2026, under docket FDA-2018-D-4533.
• It extends FDA's animal-drug compounding enforcement policy to federally-registered facilities that operate under CGMP.
• Federally-registered facilities are those registered under section 503B(b) or section 510(b) of the FD&C Act.
• Compounding an animal drug from a bulk substance still creates an unapproved new animal drug. CGMP reduces, but does not erase, the quality gap versus an approved product.
• FDA is asking ten specific questions, including whether to widen the list of eligible bulk substances, which makes this an open door for industry comment.

What GFI #256B is

What is GFI #256B? It is a draft FDA guidance that describes when the agency generally will not take enforcement action against animal drugs compounded from bulk drug substances at FDA-registered facilities that follow CGMP. It is guidance, not a regulation, so it is not binding, and alternative approaches that meet the law remain available. It was published on 28 August 2026 as document 2026-17580 in the Federal Register (91 FR 55602).

FDA's animal-drug compounding policy now spans three kinds of compounder. The table shows how the final GFI #256 and the new draft GFI #256B fit together.

GFI #256 covers pharmacists and veterinarians working in state-licensed pharmacies and in federal facilities. GFI #256B is aimed at a different operator: a facility that is registered with FDA, follows CGMP, and complies with state drug, pharmacy and veterinary laws, but that may not hold a state pharmacy licence because the state licenses it as something else, such as an outsourcing facility. FDA intends to combine the two documents once the draft is finalized, treating the changes as level 2 revisions to GFI #256.

The regulatory backdrop: why compounding from bulk is different

Why does compounding from bulk need special treatment? Under the Federal Food, Drug, and Cosmetic Act, compounding an animal drug from a bulk drug substance creates a new animal drug that has not gone through FDA approval. By law, such a drug must meet approval, CGMP and adequate-directions-for-use requirements that a compounded product does not satisfy. FDA has long used enforcement discretion to allow this compounding when no medically appropriate approved option exists.

FDA is blunt about the legal position. Under sections 512, 517 and 572 of the FD&C Act, a drug compounded from bulk substances is a new animal drug that requires approval, conditional approval or indexing. All animal drugs must also be made in accordance with CGMP under section 501(a)(2)(B), and carry adequate directions for use under section 502(f)(1). A compounded drug meets none of these. A guidance does not change the law. Instead it describes the narrow circumstances, and the animal populations, for which FDA will exercise enforcement discretion. GFI #256 did this for pharmacies and federal facilities. GFI #256B extends the same logic to registered facilities, with CGMP as the added safeguard.

What compounding under CGMP means

What does compounding under CGMP mean here? It means making the compounded animal drug in a facility that follows current good manufacturing practice, the same quality framework that applies to approved finished pharmaceuticals under 21 CFR Parts 210 and 211. CGMP brings controls for facilities, equipment, materials, testing, records and release that ordinary pharmacy compounding does not require.

FDA's argument is that CGMP narrows the quality gap. In the draft, the agency notes that production under CGMP presents fewer quality concerns than compounding under the non-CGMP conditions of GFI #256. It is careful, though, not to equate a CGMP-compounded product with an approved one. Even under CGMP, an unapproved compounded drug does not undergo the product-specific chemistry, manufacturing and controls review that an approved product completes during its application. In other words, CGMP controls how the product is made, but it does not confirm that the specific formulation is safe and effective the way an approval does. For a manufacturer, that distinction matters: adopting CGMP is not a shortcut around approval, it is a quality baseline that lowers risk while the product remains unapproved. Our walkthrough of 21 CFR 211.192 investigations shows the kind of investigation discipline CGMP expects when a result is out of specification.

Who counts as a federally-registered facility

Who is a federally-registered facility? In GFI #256B, it is a facility registered with FDA under section 503B(b) of the FD&C Act, an outsourcing facility, or under section 510(b), a conventional drug establishment. These facilities operate under state drug, pharmacy and veterinary law but may not be licensed as pharmacies. The draft's recommendations reach both outsourcing facilities and traditional animal-drug manufacturers.

This definition is the heart of the change. An outsourcing facility registered under 503B is already familiar on the human side, where such facilities compound under CGMP and are inspected on a risk basis. We covered a recent human-compounding enforcement wave in our review of FDA's compounded GLP-1 warning letters. Extending an animal-drug compounding policy to 503B(b) and 510(b) registrants brings that model into veterinary medicine. FDA notes that, to its knowledge, no facilities registered only under section 510(b) currently compound patient-specific prescriptions, so the immediate reach is mostly outsourcing facilities. Of roughly 98 federally-registered facilities that do any compounding in the United States, about eight handle both human and animal compounding, a small but strategically important group.

Scope and conditions

What can be compounded, and for which animals? The draft covers compounding animal drugs from bulk substances for nonfood-producing animals, with or without a patient-specific prescription. It also covers a narrow set of uses for food-producing animals and for wildlife, subject to conditions. The main conditions are summarized below.

• Nonfood-producing animals: compounding from bulk is covered with or without a patient-specific prescription, within the guidance's conditions.
• Food-producing animals: only certain bulk substances used as antidotes are covered, with a documented, scientifically based withdrawal time.
• Free-ranging wildlife: certain bulk substances used as sedatives or anesthetics are covered, again with residue safeguards.
• Copies of approved drugs: when the compounded drug is essentially a copy of an approved, conditionally approved or indexed drug, there should be a clinical difference for the identified patient, documented by the veterinarian.
• Office stock and the eligible-substance list: office-stock compounding for nonfood animals is tied to FDA's List of Bulk Drug Substances, and the draft asks whether that list should widen for CGMP producers.
• Labelling: compounded products should carry defined information and statements, including that the product is compounded and not FDA approved or indexed.

Why this matters to Canadian manufacturers and CMOs

Why should a Canadian firm care? Because the audience for GFI #256B includes any facility registered, or considering registration, with FDA to supply the US veterinary market. A Canadian contract manufacturer or outsourcing facility that compounds animal drugs from bulk for US customers would fall within the draft's scope, and would need to meet CGMP to rely on the policy.

The practical reading for a Canadian manufacturer is twofold. First, if you already hold or are pursuing an FDA registration under 503B(b) or 510(b) to serve US veterinary customers, GFI #256B tells you the quality bar, CGMP, and the conditions that keep you inside FDA's enforcement discretion. Second, even firms that stay on the Canadian side should note the direction of travel. Canada regulates veterinary drugs through Health Canada, and lower-risk products through the Veterinary Health Product notification programme, while the European Union has just separated veterinary GMP from human GMP. Across all three systems, the expectation that unapproved or lower-oversight products still be made under a real quality system is converging. A CGMP-capable quality system built for one market is an asset in the others.

The open questions and the comment window

What is FDA asking for? Alongside the draft, FDA poses ten specific questions and invites comment by 27 November 2026. They are a rare, direct signal of where the policy may move, and a chance for industry to shape it. The most consequential include the following.

• Whether to expand the eligible bulk substances beyond the current office-stock list for products made under CGMP.
• What share of animal drugs compounded from bulk are copies of approved or indexed products.
• Whether any parts of GFI #256 discourage making the same drugs under CGMP.
• How recent USP General Chapters 795 and 797 changes affect state-licensed pharmacies, and whether they should be able to dispense CGMP-made compounded animal drugs.
• How to prevent prescriptions for groups of animals from being misused as a route to office stock.

Firms with a stake in the US veterinary market, including Canadian exporters and their US customers, can submit comments through the docket, FDA-2018-D-4533 on Regulations.gov. A short, evidence-based comment that answers one or two of FDA's questions with real data carries more weight than a general statement. We help clients build exactly that kind of comment.

Readiness checklist

If your facility compounds, or plans to compound, animal drugs from bulk for the US market, use this checklist to gauge readiness.

• Confirm whether your facility is, or should be, registered with FDA under section 503B(b) or section 510(b).
• Map your compounded products against the definition of a copy, and document a clinical rationale where one applies.
• Check every bulk substance against FDA's List of Bulk Drug Substances for office-stock compounding in nonfood animals.
• Stand up a CGMP quality system covering facilities, equipment, materials, testing, records and batch release.
• Build out-of-specification, stability and change-control procedures that meet 21 CFR Part 211 expectations.
• Document veterinarian medical rationale and, for food animals, a scientifically based withdrawal time.
• Apply compounded-product labelling, including the statement that the product is compounded and not FDA approved.
• Separate patient-specific compounding from office stock, and define how prescriptions for groups of animals are handled.
• Prepare a docket comment before 27 November 2026 if the policy affects your business.

Common mistakes

• Assuming CGMP equals approval. CGMP controls how a product is made; it does not replace the approval that confirms a specific formulation is safe and effective.
• Treating guidance as law. GFI #256B is enforcement policy, not a rule. The underlying statute still classifies the product as an unapproved new animal drug.
• Ignoring the copy test. Compounding a near-copy of an approved product without a documented clinical difference is a common exposure.
• Overlooking withdrawal times for food animals. Antidote compounding for food-producing animals fails without a documented, scientifically based withdrawal time.
• Missing the comment window. Waiting for the final guidance forfeits the chance to shape it before 27 November 2026.

Frequently asked questions

What is FDA GFI #256B?

GFI #256B is a draft FDA guidance published on 28 August 2026 that describes when FDA does not intend to take enforcement action against animal drugs compounded from bulk drug substances at federally-registered facilities operating under CGMP. It supplements the final guidance GFI #256 and is open for comment until 27 November 2026 under docket FDA-2018-D-4533.

How is GFI #256B different from GFI #256?

GFI #256, finalized in 2022, covers compounding by veterinarians and pharmacists in state-licensed pharmacies and federal facilities, which are not required to follow CGMP. GFI #256B adds a third category, FDA-registered facilities under section 503B(b) or 510(b) that compound under CGMP. FDA plans to merge GFI #256B into GFI #256 once comments are considered.

Does GFI #256B make compounded animal drugs FDA approved?

No. Compounding an animal drug from a bulk substance still creates an unapproved new animal drug under the Federal Food, Drug, and Cosmetic Act. GFI #256B describes when FDA will exercise enforcement discretion, and CGMP lowers the quality risk, but the product is not FDA approved and must be labelled to say so.

What is a federally-registered facility?

In GFI #256B, a federally-registered facility is one registered with FDA as an outsourcing facility under section 503B(b) or as a drug establishment under section 510(b) of the FD&C Act. These facilities may operate under state law without being licensed as pharmacies, for example where the state licenses them as outsourcing facilities.

Does GFI #256B apply to Canadian companies?

It applies to any facility registered, or seeking registration, with FDA to supply the US veterinary market, which can include Canadian contract manufacturers and outsourcing facilities. Products sold only in Canada are governed by Health Canada rules, but Canadian firms serving US customers should read GFI #256B closely.

When is the comment deadline for GFI #256B?

Comments are due by 27 November 2026 to ensure FDA considers them before it finalizes the guidance. Comments can be submitted through Regulations.gov under docket FDA-2018-D-4533.

How MFLRC can help

MF License and Regulatory Consultants helps drug and animal-health manufacturers translate a new FDA guidance into an operational plan. For firms weighing an animal-drug compounding line, we run gap assessments against CGMP and the conditions in GFI #256 and #256B, build the quality management system, SOPs and batch records CGMP requires, and prepare inspection-ready investigation and out-of-specification procedures. Our audit team runs mock inspections and supplier reviews, our regulatory affairs and import and export team supports FDA registration and cross-border strategy, and we can draft an evidence-based docket comment before the deadline. We work across the pharmaceutical and veterinary sectors, from quality system design to validation and licensing.

Conclusion

GFI #256B is a small document with a clear message: FDA wants more of the compounding it tolerates to happen under a real quality system. For animal-health manufacturers, and for the Canadian contract makers who serve them, that is both a constraint and an opening. The constraint is CGMP, with everything it demands of facilities, records and testing. The opening is a defined, lower-risk path to serve veterinary needs that approved products do not meet, and a rare invitation to shape the final policy before it lands. Firms that read the draft now, measure themselves against it, and comment before 27 November 2026 will be ready when the guidance is finalized. Those that wait will inherit whatever others negotiate.

Sources and references

• US FDA, Federal Register notice for draft GFI #256B, 91 FR 55602 (28 August 2026).
• US FDA, CVM GFI #256, Compounding Animal Drugs from Bulk Drug Substances (final, 2022).
• US FDA, docket FDA-2018-D-4533 on Regulations.gov.
• US FDA, List of Bulk Drug Substances for Compounding Office Stock Drugs for Use in Nonfood-Producing Animals.
• US FDA, Animal Drug Compounding overview.
• US FDA, CGMP for finished pharmaceuticals, 21 CFR Part 211, via eCFR.