Affirmation of NY N316581; Tariff classification of APL-2, Pegcetacoplan (CAS # 2019171-69-6)

H321337 April 27, 2026 OT:RR:CTF:CPMMA H321337 GIH CATEGORY: Classification TARIFF NO.: 3907.20.0000 Mr. Herbert J. Lynch Sullivan & Lynch, P.C. 800 Turnpike Street Suite 300 North Andover, Massachusetts 01845 RE: Affirmation of NY N316581; Tariff classification of APL-2, Pegcetacoplan (CAS # 2019171-69-6) Dear Mr. Lynch: This letter is in response to your correspondence, dated September 20, 2021, in which you request reconsideration of New York Ruling Letter (NY) N316581, dated July 2, 2021 (reconsideration request). NY N316581, which was issued to Apellis Pharmaceuticals, Inc. (Apellis), involves the tariff classification of APL-2, pegcetacoplan (CAS #2019171-69-6), under the Harmonized Tariff Schedule of the United States (HTSUS). In NY N316581, U.S. Customs and Border Protection (CBP) classified the subject product under subheading 3907.20.0000, HTSUSA (Annotated) (2021), which provides for “[p]olyacetals, other polyethers and epoxide resins, in primary forms; polycarbonates, alkyd resins, polyallyl esters and other polyesters, in primary forms: other polyethers.” In your reconsideration request, you assert that the classification is incorrect, and that the pegcetacoplan is correctly classified in heading 3002, HTSUS, which provides for “[h]uman blood; animal blood prepared for therapeutic, prophylactic or diagnostic uses; antisera, other blood fractions and immunological products, whether or not modified or obtained by means of biotechnological processes; vaccines, toxins, cultures of micro-organisms (excluding yeasts) and similar products; cell cultures, whether or not modified” (emphasis added). If not classified in heading 3002, HTSUS, you assert the subject merchandise is classified in heading 3003, HTSUS, which provides for “[m]edicaments (excluding goods of heading 30.02, 30.05 or 30.06) consisting of two or more constituents which have been mixed together for therapeutic or prophylactic uses, not put up in measured doses or in forms or packings for retail sale.” Having reviewed NY N316581 and determined that it is correct, we hereby affirm NY N316581 for the reasons set forth below. The product at issue was described in NY N316581, as follows: The subject product is APL-2, also referred to as pegcetacoplan (CAS # 2019171-69-6). The product is marketed for use in clinical trials to treat various immunological diseases. You state that the product targets the part of the immune system known as the complement system. The product is formed in a single reaction between Peptide 1603 and polyethylene glycol (PEG). You note that the pegylated product is preferred because the PEG extends the half-life of the compound, allowing the APL-2 drug product to be dosed less frequently and in smaller amounts. The product will be imported into the United States as a pure bulk solid. The descriptions of the APL-2 included in your reconsideration request are consistent with those set forth above. Classification under the HTSUS is in accordance with the General Rules of Interpretation (GRIs). GRI 1 provides that the classification of goods will be determined according to the terms of the headings of the tariff schedule and any relative section or chapter notes. In the event that the goods cannot be classified solely on the basis of GRI 1, and if the headings and legal notes do not otherwise require, the remaining GRIs 2 through 6 will then be applied in order. The Explanatory Notes (ENs), although neither dispositive nor legally binding, provide a commentary on the scope of each heading of the HTSUS, and are the official interpretation of the Harmonized System at the international level. See T.D. 89-80, 54 Fed. Reg. 35127, 35128 (Aug. 23, 1989). You argue that APL-2 (pegcetacoplan) is classifiable in heading 3002, HTSUS, because it is an immunological product consisting of a pegylated synthetic cyclic peptide. Heading 3002, HTSUS, provides for, among other goods, “immunological products, whether or not modified or obtained by means of biotechnological processes.” Note 2 to Chapter 30 of the HTSUS defines “immunological products,” noting that for the purposes of heading 3002, HTSUS: … the expression “immunological products” applies to peptides and proteins (other than goods of heading 29.37) which are directly involved in the regulation of immunological processes, such as monoclonal antibodies (MAB), antibody fragments, antibody conjugates and antibody fragment conjugates, interleukins, interferons (IFN), chemokines and certain tumor necrosis factors (TNF), growth factors (GF), hematopoietins and colony stimulating factors (CSF). Although APL-2 is a peptide that interacts with the immune system, the subject drug does not directly regulate an immunological process. For the purposes of heading 3002, HTSUS, “directly involved in the regulation of immunological processes” generally refers to a process by which an endogenous chemical or biological molecule, in furtherance of the goal of bodily defense, modifies or controls the immune system. In Lab Reports NY 20210073 and NY20211581, CBP Laboratories and Scientific Services Directorate (LSSD) indicated that while the APL-2 interacts with the innate immune system, its synthetic peptide sequence inhibits the complementary system by binding specifically to C3 and does not directly regulate an immunological process. Therefore, we find that APL-2 cannot be an immunological product of heading 3002, HTSUS, because it does not directly regulate an immunological process. 2 If not classified in heading 3002, HTSUS, you argue for classification under heading 3003, HTSUS, which provides for “[m]edicaments (excluding goods of heading 3002, 3005 or 3006) consisting of two or more constituents which have been mixed together for therapeutic or prophylactic uses, not put up in measured doses or in forms or packings for retail sale.” Note 3 to Chapter 30 states that for the purposes of heading 30.03: The following are to be treated: (a) As unmixed products: (1) Unmixed products dissolved in water; (2) All goods of Chapter 28 or 29; and (3) Simple vegetable extracts of heading 13.02, merely standardised or dissolved in any solvent; (b) As products which have been mixed: (1) Colloidal solutions and suspensions (other than colloidal sulphur); (2) Vegetable extracts obtained by the treatment of mixtures of vegetable materials; and (3) Salts and concentrates obtained by evaporating natural mineral waters. The ENs for heading 3003, HTSUS, also emphasize that the heading covers preparations obtained by mixing two or more constituents, including “preparations containing a single pharmaceutical substance together with an excipient, sweetening agent, agglomerating agent, support, etc.” Therefore, for APL-2 to be classified in heading 3003, HTSUS, it must consist of at least two separate constituents. In your request for reconsideration, you describe the subject merchandise as “the result of the mixture/bonding of peptide 1603 with polyethylene glycol,” which satisfies the requirement of multiple constituents as contemplated by Heading 3003, HTSUS. Specifically, you state that peptide 1603 is the active pharmaceutical ingredient and the polyethylene glycol is included to extend the systemic half-life of the drug; they are separately identifiable constituents and their bonding represents a mixing. However, in your original ruling request, you argued that APL-2 is unmixed for the purposes of heading 3003, HTSUS, because at time of importation it is a pure bulk solid, without excipients or liquids. During our review, LSSD confirmed that APL-2 is formed in a single chemical reaction and is comprised of two identical peptides covalently bound to a PEG moiety. The active pharmaceutical ingredient is the totality of the peptide and PEG portions of the product chemically connected. The pegcetacoplan is not a separate, chemically defined organic compound and its composition is not defined by a constant ratio of elements; it cannot be represented by a definitive structural diagram. Nor is it a preparation containing a single pharmaceutical substance together with an excipient, sweetening agent, agglomerating agent, or support. Thus, the APL-2 is a single constituent that is unmixed and the peptide 1603 is not merely combined or mixed with the polyethylene glycol, but rather it is covalently linked by chemical reaction. Therefore, the APL-2 is a single constituent and cannot be considered to be a mixed medicament of heading 3003, HTSUS. 3 Seeing as the APL-2 is precluded from classification in headings 3002 and 3003, HTSUS, we turn next to heading 3907, HTSUS. Heading 3907, HTSUS provides for “[p]olyacetals, other polyethers and epoxide resins, in primary forms; polycarbonates, alkyd resins, polyallyl esters and other polyesters, in primary forms.” The ENs to heading 3907 instruct that heading includes pegylated derivatives of products of Chapter 29; however, “pegylated products whose non-pegylated forms are classifiable in Chapter 29 (Headings 2936 to 2939 and 2941) or in Chapter 30 are excluded from classification in Heading 3907.” There is no dispute that APL-2 is PEGylated.1 A compound is considered PEGylated when a protein or peptide is covalently linked with polyethene glycol (PEGylation). Here, peptide 1603 is reacted with the polyethene glycol resulting in the creation of the entire compound – pegcetacoplan. Therefore, we must look to the applicable heading of the APL-2’s non-pegylated form. Heading 2934, HTSUS, provides for “Nucleic acids and their salts, whether or not chemically defined; other heterocyclic compounds.” The Explanatory Notes (ENs) to Chapter 29 provide: This Chapter further includes pegylated (polyethylene glycol (or PEGs) polymers) derivatives of products of headings 29.36 to 29.39 and 29.41. For these products, a pegylated derivative remains classified in the same heading as its non-pegylated form. However, pegylated derivatives of products of all other headings of Chapter 29 are excluded (generally heading 39.07). Based on APL-2’s chemical structure2, the correct classification for the non-PEGylated product (peptide 1603) would be in heading 2934, HTSUS, which provides for “[n]ucleic acids and their salts, whether or not chemically defined; other heterocyclic compounds: Other: Other: Aromatic or modified aromatic: Other: Drugs.” Since the peptide 1603 is reacted with the polyethene glycol, then the entire compound (pegcetacoplan) is classified in heading 3907 based on the PEG. Accordingly, by application of GRI 1, the subject APL-2 (pegcetacoplan) is properly classified in heading 3907, HTSUS, as “[p]olyacetals, other polyethers and epoxide resins, in primary forms; polycarbonates, alkyd resins, polyallyl esters and other polyesters, in primary forms. Specifically, the APL-2 is classified in subheading 3907.0.0000, HTSUSA which provides for polyacetals, other polyethers and epoxide resins, in primary forms; polycarbonates, alkyd resins, polyallyl esters and other polyesters, in primary forms: other polyethers. The column 1, general rate of duty is 6.5 percent ad valorem. 1 See Francesco A. Vernose & Anna Mero, The impact of PEGylation on biological therapies National Library of Medicine, BIODRUGS, https://pubmed.ncbi. nlm.nih. gov/18778113/. 2 NY Lab Report NY20211581 states the APL-2 drug substance’s chemical structure consists of carbamate, carboxamide, carboxylic acid, ether, alcohol, nitrogen containing heterocycle (unfused imidazole and fused pyrrole), other heterocycle (containing nitrogen and sulfur), and polyether functional groups. 4 Duty rates are provided for your convenience and are subject to change. The text of the most recent HTSUS and the accompanying duty rates are provided online at: https://hts.usitc.gov. Sincerely, Yuliya A. Gulis, Director Commercial and Trade Facilitation Division 5