CLA-2 RR:CR:GC 966670 AM
Mr. Sean T. Murray
Miller & Company
4929 Main Street
Kansas City, MO 64112
Re: Long™ R3 IGF-1 ; NY F80635
Dear Mr. Murray:
This is in reference to your letter, dated August 14, 2003, on behalf of JRH Biosciences, concerning the classification, under the Harmonized Tariff Schedule of the United States, (HTSUS), of Long™ R3 IGF-1.
In preparing our response, we have also reviewed New York Ruling (NY) F80635, dated July 13, 2000. That ruling classifies Long™ R3 IGF-1 under heading 2933, HTSUS (2000), the provision for heterocyclic compounds with nitrogen hetero-atoms only. We declined to classify the product in heading 2937, HTSUS (2000), the provision for hormones and derivatives used as hormones, because the product “is not used as a hormone (i.e., to inhibit or stimulate the functioning of particular organs). Rather, it is used in vitro as a growth stimulant in tissue culture.”
You ask that, in light of recent changes to the text of heading 2937, HTSUS (2003), we now classify the merchandise in that heading, the provision for derivatives and structural analogues of hormones used primarily as hormones.
FACTS:
According to counsel, Long™ R3 IGF-1 is a protein containing 83 amino-acid residues, constructed by taking IGF-1, substituting the third amino-acid residue, glutamate, for arginine, and adding 13 additional amino-acid residues to the IGF-1 polypeptide molecule. Long™ R3 IGF-1 produces the same biological responses as insulin in that it is a mediator of anabolic and mitogenic activity and is used in place of insulin in cell culture applications.
Insulin-like Growth Factors (“IGF’s”) are hormones structurally related to insulin which indirectly mediate the anabolic and growth-promoting effects of growth hormones. IGFs are produced primarily in the liver under the regulation of growth hormones but are also produced locally by most tissues. Goodman & Gilman’s The Pharmaceutical Basis of Therapeutics, Tenth Ed., McGraw-Hill Companies, 2001, p. 1545.
ISSUE:
Is Long™ R3 IGF, as used in cell culture, a hormone derivative or hormone analogue used primarily as a hormone?
LAW AND ANALYSIS:
Merchandise imported into the U.S. is classified under the HTSUS. Tariff classification is governed by the principles set forth in the General Rules of Interpretation (GRIs) and, in the absence of special language or context which requires otherwise, by the Additional U.S. Rules of Interpretation. The GRIs and the Additional U.S. Rules of Interpretation are part of the HTSUS and are to be considered statutory provisions of law.
GRI 1 requires that classification be determined first according to the terms of the headings of the tariff schedule and any relative section or chapter notes and, unless otherwise required, according to the remaining GRIs taken in order. GRI 6 requires that the classification of goods in the subheadings of headings shall be determined according to the terms of those subheadings, any related subheading notes and mutatis mutandis, to the GRIs.
In understanding the language of the HTSUS, the Explanatory Notes (ENs) of the Harmonized Commodity Description and Coding System may be utilized. The ENs, although not dispositive or legally binding, provide a commentary on the scope of each heading, and are generally indicative of the proper interpretation of the HTSUS. See, T.D. 89-80, 54 Fed. Reg. 35127 (August 23, 1989).
The following provisions of the HTSUS are under consideration:
Heterocyclic compounds with nitrogen hetero-atom(s) only:
Other:
Other:
Aromatic or modified aromatic:
Other:
Other:
2933.99.79 Products described in additional U.S. note 3 to section VI
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Hormones, prostaglandins, thromboxanes and leukotrienes, natural or reproduced by synthesis; derivatives and structural analogues thereof, including chain modified polypeptides, used primarily as hormones:
Polypeptide hormones, protein hormones and glycoprotein hormones, their derivatives and structural analogues:
2937.19.00 Other
The EN (2002) to Sub-Chapter XI of Chapter 29, which includes heading 2937, HTSUS, states: "[I]n this Sub-Chapter, the term "derivatives" refers to chemical compounds which could be obtained from a starting compound of the heading concerned and which retain the essential characteristics of the parent compound, including its basic chemical structure."
EN 29.37 (2002), states, in pertinent part, the following:
This heading includes :
* * * *
(IV) Derivatives of natural or synthetically reproduced hormones, prostaglandins, thromboxanes and leukotrienes, such as salts, halogenated derivatives, cyclic acetals, esters, etc., including mixed derivatives (e.g., esters of halogenated derivatives), provided that they are used primarily as hormones.
(V) Analogues of hormones, prostaglandins, thromboxanes and leukotrienes. The term “analogue” refers to chemicals having a close structural relationship to the parent compound, but which are not considered to be derivatives. It includes compounds which have a structural resemblance to the natural compounds, but have had one or more atoms in the structure replaced by others.
Analogues of polypeptide hormones are formed by adding, separating, replacing or altering certain amino acids in the natural polypeptide chain. Somatrem (INN), an analogue of the growth hormone somatotropin, is the result of adding a terminal amino acid to the natural somatotropin molecule. Ornipressin (INN), an analogue of natural argipressin (INN) and lypressin (INN), is the result of replacing an internal amino acid in the argipressin or lypressin molecule. The synthetic gonadoliberins, buserelin (INN), nafarelin (INN), fertirelin (INN), leuprorelin (INN) and lutrelin (INN), analogues of gonadorelin (INN) are the result of altering and replacing certain amino acids in the polypeptide chain of natural gonadorelin. Giractide (INN), an analogue of corticotropin (INN) has the same structure as the first 18 amino acids of natural corticotropin, with the first amino acid replaced. Metreleptin (INN), an analogue of leptin, is the recombinant methionyl derivative of human leptin. Saralasin (INN), which contains three different amino acids in comparison to the molecule of angiotensin II, should be considered as a structural analogue of angiotensin II, although with antagonist effects (the former is a hypotensor and the latter an hypertensor).
* * * *
. . . .The heading also includes derivatives and structural analogues of hormones, provided that they are based on natural hormones, or on those reproduced by synthesis, and that they act using mechanisms similar to those of hormones.
[all emphasis in the original]
* * * * *
In 2000, heading 2937, HTSUS, was the provision for "Hormones, natural or reproduced by synthesis; derivatives thereof, used primarily as hormones; other steroids used primarily as hormones." The heading text at the time NY F80635 was promulgated did not explicitly include structural analogues of hormones. In fact, you state in your submission that an employee of the International Trade Commission (ITC) revealed to you that "the ITC indicated that the scope of Heading 2937 was expanded because the Harmonized System Committee (HSC) found that the heading structure was out of date and too restrictive. It determined that this heading should logically cover, in addition to hormones, synthetic hormone analogues and derivatives that the old language did not explicitly include." Hence, provided the instant merchandise is used as a hormone, it could be included in the terms of heading 2937 (2003) as an analogue, but not in the terms of heading 2937 (2000).
We find that contrary to the statement made in NY F80635, the instant merchandise is used as a hormone when used in cell culture because, like insulin, it is a mediator of anabolic and mitogenic activity in cell culture applications.
However, the instant merchandise is produced partially from the substitution of arginine for glutamate at the third amino-acid residue. As such, it is not a derivative of IGF-1 because it does not retain the basic structure of the parent compound as prescribed by the EN. Therefore, NY F80635 came to the correct conclusion under the HTSUS (2000), that Long™ R3 IGF-1 cannot be classified in heading 2937, albeit for the incorrect reason dealing with use, rather than the correct explanation as to its chemical structure being other than that of a derivative of a hormone.
Yet, the instant merchandise is referred to in the literature as an analogue of IGF-1. It is based on the natural hormone IGF-1 and retains its functionality. It is created, as described above, by the substitution of one amino-acid residue in the polypeptide chain for another, and the addition of thirteen other amino-acid residues to the polypeptide chain. Therefore, as of the adoption of Presidential Proclamation 7515, dated December 18, 2001, adopting the amendments promulgated by the ITC to the HTSUS (2002), Long™ R3 IGF-1 is classified in subheading 2937.19.00, HTSUS, the provision for "Hormones, prostaglandins, thromboxanes and leukotrienes, natural or reproduced by synthesis; derivatives and structural analogues thereof, including chain modified polypeptides, used primarily as hormones: Polypeptide hormones, protein hormones and glycoprotein hormones, their derivatives and structural analogues: Other."
HOLDING:
Based on the foregoing, Long™ R3 IGF-1 is classified in subheading 2937.19.00, HTSUS, the provision for "Hormones, prostaglandins, thromboxanes and leukotrienes, natural or reproduced by synthesis; derivatives and structural analogues thereof, including chain modified polypeptides, used primarily as hormones: Polypeptide hormones, protein hormones and glycoprotein hormones, their derivatives and structural analogues: Other."
EFFECT ON OTHER RULINGS:
NY F80635 is revoked by operation of law pursuant to Presidential Proclamation 7515, dated December 18, 2001.
Sincerely,
Myles B. Harmon, Director
Commercial Rulings Division