On September 30, 2025, the U.S. District Court for the Southern District of Indiana issued a decision vacating the decision by the Food and Drug Administration (FDA) to regulate Eli Lilly's "retatrutide" product as a drug rather than a biological product. The decision is potentially significant because the court rejected the FDA's narrow interpretation of "analogous" to a protein category, which the FDA has read restrictively to preserve its bright-line definition of a "protein." As a result, the FDA may be led to group a broader range of products within the "biological product" category, which is subject to the distinct licensure process under the Public Health Service Act as compared to the process for drug approvals under the Federal Food, Drug, and Cosmetic Act.
By way of background, in the Biologics Price Competition and Innovation Act of 2009, Congress amended the PHSA definition of "biological product" to include "protein" (i.e., "a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product [...] applicable to the prevention, treatment, or cure of a disease or condition of human beings"1). In 2020, the FDA finalized a rule adopting a regulatory definition for the "protein" category. That definition provides:
(6) A protein is any alpha amino acid polymer with a specific, defined sequence that is greater than 40 amino acids in size. When two or more amino acid chains in an amino acid polymer are associated with each other in a manner that occurs in nature, the size of the amino acid polymer for purposes of this paragraph (h)(6) will be based on the total number of amino acids in those chains, and will not be limited to the number of amino acids in a contiguous sequence.2
In adopting this regulatory definition of "protein," the FDA expressly declined to also adopt a definition for the "analogous" to a protein category. Instead, the agency advised only that products that do not satisfy the bright-line requirements for the protein definition (i.e., "specific, defined sequence" and "greater than 40 [alpha] amino acids") also do not qualify as "analogous" products. Rather, the FDA regarded the "analogous" category as a narrow, residual category that could apply to, for example, naturally derived mixtures that include proteins as one component among others.
Companies have challenged the FDA's implementation of its rule for proteins, including the agency's interpretation of the "analogous" product category. But initial challenges were brought at a time when agency interpretations of statutes were still entitled to deference under the Chevron doctrine and courts ruled in favor of the FDA.3
This most recent litigation involves Lilly's retatrutide product, which consists of a chain of 39 alpha amino acids and a second associated chain of two amino acids (at least one of which is not an alpha amino acid) covalently bonded to the first chain. The FDA concluded that the product should be regulated as a drug because, together, its chains neither meet the definition of a protein, which requires the relevant polymer to contain more than 40 alpha amino acids, nor constitute a product "analogous" to a protein because it "does not share the 'fundamental defining property' of [a protein] of being greater than forty alpha amino acids in size." The District Court upheld the FDA's conclusion that Lilly's product is not a protein on the ground that the regulatory definition provides that only alpha amino acids count. But the court rejected the FDA's interpretation of "analogous" product.
In reaching that decision, the District Court concluded that the "FDA's 'bright line' approach" to the analogous product category "flouts the statutory text and sidesteps congressional intent" because Congress necessarily adopted the "analogous" product category to capture products that do not already fit into the other distinct categories, including "protein." The court recognized that the FDA "may have a degree of flexibility in determining the threshold for scientific similarity" but instructed that such a "threshold must be clearly defined and consistently applied." The court thus set aside the FDA's decision and remanded for the agency "to identify, in a uniform fashion, the fundamental defining feature of 'analogous' proteins." The court's decision leaves open the possibility that the FDA could reaffirm its decision that retatrutide is not a biological product under a proper definition of "analogous."
The decision also opens up the possibility that the FDA may be required to adopt a more expansive approach to the category of products that are analogous to proteins, which, among other things, would have significant implications for the available approval pathways for generic or biosimilar products. As the District Court decision was just issued, the FDA has not yet provided any public guidance regarding the timing or process for developing a new definition for "analogous" products.
We would like to thank Cassie Snyder for their assistance with this insight.
Footnotes
3 Refer to Ipsen Biopharmaceuticals, Inc. v. Becerra, 108 F.4th 836 (D.C. Cir. 2024) and Teva Pharmaceuticals USA, Inc. v. FDA, 514 F. Supp. 3d 66 (2020).
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