On September 18, 2026, the U.S. Food and Drug Administration (FDA) issued a Warning Letter to Empower Clinic Services, LLC (dba Empower Pharmacy) addressing its compounding of tirzepatide and semaglutide combination products. The Letter is directly relevant to pharmacies that compound glucagon-like peptide-1 (GLP-1) products with added ingredients, including vitamin B12 or niacinamide. In the Letter, the FDA concluded that such co-formulations remained “essentially copies” of FDA-approved semaglutide and tirzepatide products, notwithstanding the added ingredient. The FDA further stated that the volume of products produced suggests that differences between the products being compounded and the FDA-approved products are pretextual.
This appears to be the first time FDA has invoked the term “pretextual” compounding in the context of GLP-1 coformulations in a Warning Letter. FDA supported this conclusion by pointing to monthly production volumes for both tirzepatide and semaglutide products, though the specific figures were redacted in the published Letter. FDA separately scrutinized how “significant difference” determinations were documented, specifically flagging templated language and third-party technology platforms that present prescribers with pre-selected options.
Regulatory Background: The “Essentially a Copy” Standard
Section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act) exempts drugs compounded by a licensed pharmacist or physician for an identified individual patient from three requirements that otherwise apply to drugs: FDA premarket approval, adequate-directions-for-use labeling, and current good manufacturing practice (CGMP) requirements. One condition of that exemption is that the compounder not regularly compound, or compound in inordinate amounts, drug products that are “essentially copies” of a commercially available drug product.
Under FDA’s January 2018 guidance, a compounded product is generally treated as essentially a copy if it (i) contains the same active pharmaceutical ingredient(s) (APIs) as a commercially available product; (ii) is in the same, similar, or easily substitutable strength; and (iii) can be administered by the same route, unless the prescriber documents that a change made for a specific patient produces a significant difference for that patient. The guidance further explains that where a claimed “significant difference” is a mere pretext for compounding what is otherwise essentially a copy, the compounding does not qualify for the exemption if it is done regularly or in inordinate amounts. Separately, as a matter of enforcement policy, FDA has stated it generally does not intend to pursue this issue where a compounder fills four or fewer prescriptions of a given compounded drug product per calendar month.
The FDA’s April 2026 Policy Clarification
On April 1, 2026, the FDA updated its GLP-1 compounding policy guidance to remind 503A pharmacies and 503B outsourcing facilities of the conditions applicable to compounded drugs as the national GLP-1 supply stabilized. Notably, the FDA used a semaglutide-plus-vitamin-B12 combination as its own illustrative example of a product that may be considered “essentially a copy,” despite the added ingredient, where the combination is administered by the same route and the strength of each API is within 10% of the corresponding commercially available product. The example closely resembles the combination-product issues the FDA has now raised in the Empower Warning Letter.
Compounders and prescribers have often cited legitimate clinical reasons for co-formulating GLP-1 medications with additional ingredients. For example, physicians have reported prescribing vitamin B6 (pyridoxine) to help address nausea associated with tirzepatide or semaglutide therapy, niacin (vitamin B3) to support energy metabolism and reduce fatigue, and glycine to help patients preserve lean muscle mass during weight loss. Proponents of these practices maintain that such co-formulations can reflect genuine, physician-directed clinical judgment consistent with the “significant difference” standard under section 503A(b)(2), rather than an attempt to work around FDA’s essentially-a-copy restriction.
The Empower Warning Letter
Following a November 2025 inspection, the FDA’s September 18, 2026, Warning Letter found that Empower’s tirzepatide/niacinamide and semaglutide/cyanocobalamin products appeared to be essentially copies of FDA-approved semaglutide and tirzepatide products, notwithstanding the added ingredient. Two aspects of the Letter are particularly significant for compounding pharmacies, prescribers, and telehealth platforms.
Volume as evidence of pretext.
The FDA stated that “[t]he volume of products you are producing suggests that differences between products you are compounding and the FDA-approved products are pretextual,” citing monthly order counts (the specific figures were redacted in the published Letter) across several months for three products. This appears to be the first instance, to our knowledge, of the FDA expressly invoking a “pretextual” framing in a Warning Letter to support an “essentially a copy” finding, language that closely tracks arguments previously advanced by Eli Lilly and Novo Nordisk in private litigation against compounders and telehealth platforms.
Documentation practices.
The FDA separately found that Empower’s records reflected: (1) prescriptions with no prescriber determination of significant difference at all; (2) significant-difference language repeated verbatim across many records, suggesting the language was pre-generated for selection rather than individually written for a specific patient; and (3) high order volume for the same products. The FDA stated that generating prescriptions through means that undermine the individualized nature of a prescriber’s clinical judgment, including third-party technology platforms that present prescribers with pre-selected menu options for a significant-difference statement, calls into question whether the resulting determinations satisfy conditions of section 503A.
The Letter also cited insanitary conditions and CGMP deficiencies, including issues involving aseptic processing controls, media fills, and environmental monitoring, and found Empower’s corrective-action response insufficiently documented in several respects, including unreconciled media fill vial counts and undocumented data transcription between forms.
Broader Enforcement Context
This Letter arrives amid an increasingly active enforcement and litigation environment for compounders of GLP-1 products:
- Enforcement discretion tied to the semaglutide and tirzepatide shortages ended in 2025 for both 503A pharmacies and 503B outsourcing facilities.
- On April 30, 2026, the FDA proposed excluding semaglutide, tirzepatide, and liraglutide from the 503B bulks list, which, if finalized, would foreclose bulk compounding of these products by outsourcing facilities absent a new shortage designation.
- Eli Lilly and Novo Nordisk have filed numerous lawsuits against compounding pharmacies, medical spas, and telehealth platforms, frequently arguing that “personalized” or “significant difference” claims are pretextual where compounding occurs at scale using standardized processes.
Practical Takeaways
- Compounding GLP-1 combination products (e.g., with B12 or niacinamide) is not, by itself, sufficient to avoid “essentially a copy” status. The added ingredient must produce a genuine, patient-specific significant difference, and that determination must be documented.
- Boilerplate or templated significant-difference language, particularly language generated or selected through a technology platform’s pre-set menu, is a specific point of FDA scrutiny and warrants review.
- Production volume is now being cited by the FDA as independent evidence that significant-difference determinations are pretextual, separate from any documentation deficiency.
- Given the pace of enforcement activity, pharmacies should expect continued Warning Letters and litigation on this theory and should consider reviewing documentation practices and technology platform workflows proactively.
How Frier Levitt Can Help
Frier Levitt advises compounding pharmacies, outsourcing facilities, prescribers, telehealth companies, and other healthcare and life sciences businesses on FDA compliance and the evolving regulatory landscape for compounded GLP-1 products. Our attorneys can assist clients in evaluating whether current formulations and prescribing practices comply with Sections 503A and 503B, reviewing “significant difference” documentation and technology-enabled prescribing workflows, responding to FDA inspections and Warning Letters, and assessing regulatory and litigation risk related to compounded semaglutide, tirzepatide, and other GLP-1 products.
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