FDA clarifies the 'essentially a copy' rule and a four-prescription threshold

The FDA published an update on April 1, 2026 that restates and sharpens how the agency decides whether a compounded drug is "essentially a copy" of a commercially available product — and says that, for now, it does not intend to act against a pharmacy that fills four or fewer prescriptions of such a product in a calendar month ^[1].

The "essentially a copy" rule sits at the center of the compounded GLP-1 market. Federal law lets state-licensed pharmacies and physicians compound under section 503A of the Food, Drug, and Cosmetic Act only if they do not compound, regularly or in inordinate amounts, drugs that are essentially copies of commercially available products, and only for an individual patient based on a prescription ^[1].

What the guidance says

FDA says it intends to treat a compounded product as essentially a copy when it has the same active ingredient as a commercially available drug in the same, similar, or an easily substitutable strength, and the commercial product can be used by the same route of administration that was prescribed for the compounded version — regardless of how the commercial product is labeled ^[1]. The exception is when a prescriber determines and documents that the compounded product contains a change that produces a significant difference for an identified individual patient ^[1].

The update extends the same logic to combination products. A compounded drug can be considered essentially a copy if it contains the same active ingredients as two or more commercially available products in the same, similar, or easily substitutable strength, used by the same route, again absent a documented prescriber determination of a significant difference ^[1].

Then comes the worked example. FDA writes that it may consider a compounded product combining semaglutide with another active ingredient, such as vitamin B12 (cyanocobalamin), to be essentially a copy when the products are given the same way — for instance, both injectable — and when the amounts of semaglutide and vitamin B12 in the compounded product are within 10% of the strengths of the respective commercially available products ^[1]. That 10% figure is the most concrete number in the document, and it gives compounders and prescribers a specific line to measure against.

The four-prescription threshold is separate. FDA states that at this time it does not intend to take action against a compounder for compounding an essentially-a-copy product "regularly or in inordinate amounts" if the compounder fills four or fewer prescriptions of that compounded drug product during a calendar month ^[1]. The agency frames this as its current enforcement intention, not a change in the underlying law.

For outsourcing facilities operating under section 503B, the update repeats a stricter limit: they cannot compound from bulk drug substances unless the substance is on the 503B bulks list, or the drug is on FDA's shortage list at the time of compounding, distribution and dispensing. FDA states plainly that tirzepatide and semaglutide do not currently appear on either list ^[1].

Why it matters for patients

The practical effect is that large-scale compounded semaglutide and tirzepatide remain outside what FDA says it will tolerate. The shortages that opened the door closed some time ago: FDA declared the tirzepatide injection shortage resolved on December 19, 2024, and the semaglutide injection shortage resolved on February 21, 2025, with 503A enforcement discretion ending April 22, 2025, and 503B discretion ending May 22, 2025 for semaglutide ^[1].

Anyone who has been getting a compounded semaglutide-plus-B12 injection now has a clearer picture of where it stands. If the semaglutide and B12 amounts fall within 10% of the approved products' strengths and the route is the same, FDA may view it as a copy — unless a prescriber has documented a significant difference for that specific patient ^[1]. And a pharmacy that fills more than four such prescriptions in a month falls outside the stated enforcement threshold ^[1].

The update does not say how FDA will verify prescription counts, how prescriber documentation will be reviewed, or whether the four-prescription policy has an end date. Those details are not in the document. FDA also notes it may still act on other violations, such as findings that a product is of substandard quality or otherwise unsafe ^[1].