CLA-2 OT:RR:CTF:TCM H040735 ARM
Mr. Matthew T. McGrath
Barnes Richardson
11 Dupont Circle, NW, Suite 500
Washington, DC 20036
RE: Country of Origin Marking for imports of Needle-Free Injection Device with Drug Dose: Sumatriptan DosePro™
Dear Mr. McGrath:
This is in response to your request, dated October 3, 2008, on behalf of your client, Zogenix, Inc. (“Zogenix”), for a prospective ruling regarding the country of origin marking of Sumatriptan DosePro. The product is a pre-filled disposable needle-free delivery system of Sumatriptan, currently undergoing review by the Food and Drug Administration (“FDA”) for the treatment of migraine headaches.
FACTS:
Sumatriptan DosePro™ is a single dose of sumatriptan succinate from India contained in a single use jet-injection device. In the UK, the Sumatriptan succinate, imported in bulk form from India, is compounded with sodium chloride and water from the UK using helium USP for a processing aid to reduce dissolved air. The bulk formulation is then transferred to an asceptic suite through a series of sterilizing filters and is filled into an empty capsule subassembly and sealed with a sterile stopper. The empty capsule subassembly is assembled in the UK from glass capsules manufactured in Germany, pistons manufactured in the UK, interface seals manufactured in France, stoppers manufactured in the US, and capsule sleeves manufactured in Germany
An actuator subassembly is assembled in Ireland, using latches, rams, O-rings, chambers and chamber damping fluid made in the UK and couplings made in Germany, and other components consisting of the collar, caps, lever, and cover. This subassembly is also imported into the UK for assembly into the DosePro™ unit.
The DosePro jet-injection apparatus consists of these two subassemblies: the drug capsule subassembly, which contains the dose of sumatriptan succinate from India, and the actuator subassembly, which consist of a nitrogen gas powered ram and piston.
LAW AND ANALYSIS:
The marking statute, section 304, Tariff Act of 1930, as amended (19 U.S.C. 1304), provides that, unless excepted, every article of foreign origin (or its container) imported into the U.S. shall be marked in a conspicuous place as legibly, indelibly and permanently as the nature of the article (or its container) will permit, in such a manner as to indicate to the ultimate purchaser in the United States the English name of the country of origin of the article. Part 134, Customs Regulations (19 CFR Part 134) implements the country of origin marking requirements and exceptions of 19 U.S.C. 1304.
Section 134.1(b), Customs Regulations (19 CFR 134.1(b)), defines "country of origin" as:
the country of manufacture, production, or growth of any article of foreign origin entering the United States. Further work or material added to an article in another country must effect a substantial transformation in order to render such other country the "country of origin" within the meaning of this part; . . . .
A substantial transformation occurs when an article emerges from a process with a new name, character or use different from that possessed by the article prior to processing. A substantial transformation will not result from a minor manufacturing or combining process that leaves the identity of the article intact. See United States v. Gibson Thomsen Co, 27 CCPA 267 (1940) and National Juice Products Association v. United States, 628 F. Supp. 978 (Ct. Int’l Trade 1986).
CBP has considered the substantial transformation of pharmaceutical products in numerous rulings. In New York Ruling (NY) E83145, dated June 18, 1999, CBP considered the marking of an ophthalmic solution supplied in a plastic dispenser with a controlled drop tip. In that case, one active ingredient manufactured in the U.S. was combined with another active ingredient in France, packaged and imported back to the U.S. CBP found that the product had undergone a substantial transformation in France through the combining of the active ingredients in a two-drug formulation thus acquiring a new name and character. (See also Headquarter’s Ruling Letter (HQ) 563207, dated June 1, 2005).
In HQ 563301, dated August 26, 2005, CBP found that the parathormone undergoes a substantial transformation as a result of the further processing in Germany. which includes thawing the raw material; testing and adjusting the amount of active ingredient as necessary; mixing the material in a buffer solution; applying nitrogen gas to eliminate possible degradation; filtering the material through a microbial filter, and a three-step freeze drying process.
That case was likened to HQ 731731, dated February 23, 1989, where CBP found that a substantial transformation resulted when vancomycin hydrochloride imported in bulk powder form was processed in the United States into Sterile Vancomycin Hydrochloride USP, an antibiotic capable of intravenous injection. The U.S. processing was extensive and involved the following operations: (1) testing for potency and, if potency is not adequate, adding more active ingredient; (2) applying nitrogen gas to eliminate possible degradation; (3) dissolving the product into a solution; (4) filtering the solution through a special microbial filter; (5) testing for pyrogenicity; (6) placing the solution into glass vials; and (7) freeze drying the product in a three-step process—freezing to minus 40 degrees centigrade, gradual heating under extreme vacuum conditions, and extracting water.
However, in HRL 561975, dated April 3, 2002, CBP found that no substantial transformation resulted from the U.S. processing of the anesthetic drug sevoflurane. The U.S. operations in that case involved processing the drug from bulk form into measured doses, extensive testing, and filtering and packaging the product into bottles. In determining that there was no substantial transformation, CBP noted that there was no change in name (the packaged product was identified as sevoflurane on the label, with the trade name "Ultrane"), little change in the character, and no change in use of the product.
In HRL 561544, dated May 1, 2000, CBP determined that there was no substantial transformation when imported geneticin sulfate was processed into Geneticin Selective Antibiotic. The U.S. processing involved extensive testing, dissolving of the material into a solution by adding purified water, removing contaminants by filtering the solution through sterilizing grade filters, and pumping the resulting Geneticin antibiotic into sterile bottles for use in molecular genetics experiments. CBP held that no substantial transformation results from the U.S. processing as it essentially consists of the removal of impurities from the bulk chemical, and the placement of the chemical into smaller packaging.
In HQ 561975, dated April 3, 2002, an anesthetic drug imported in bulk form from Japan and processed in the U.S. into dosage form did not impart a substantial transformation of the product. See also, HQ 735146, dated November 15, 1993. The case is specifically distinguished from HQ 731731, where the addition of active ingredient, freeze drying and other substantial operations performed on bulk vancomycin hydrochloride were held to impart a substantial transformation on the product.
Lastly, in NY C85112, dated March 27, 1998, CBP considered the country of origin marking of a single-dose administration kit of leuprolide acetate for depot suspension. The active ingredient, a synthetic analog of Leuteinizing Hormone-Releasing Hormone), is exported from the U.S. to Japan, where it is encapsulated into sterile mircrospheres. These microspheres are placed in a dual-chamber syringe, where the second chamber is filled with sterile diluent. The prefilled dual-chamber syringes are packed with plastic plungers for shipment to the U.S. The microencapsulating of the leuprolide acetate modifies the delivery rate of the drug into the body from the daily-dosage form. CBP found that the fundamental character of the leuprolide acetate remained unchanged by the processing, and the country of origin of the packaged prefilled dual-chamber syringes remained the U.S.
From these rulings, we see that a substantial transformation does not occur from packaging an active ingredient in dosage form, and that generally, a substantial transformation occurs when the active ingredient is combined with other active ingredients, thereby creating a different pharmaceutical product, or calibrated with more active ingredient from another source. You argue instead, that HQ 731731 should be used as the model for substantial transformation in this case, because here, the active ingredient is combined with exipients and placed within a highly complex, single-use delivery device with a separate chemically-charged injection means. Furthermore, you state that the value added in the manufacturing operation in the UK is over 100 times greater than the value of the active ingredient.
While we agree that the injection system is sophisticated and valuable, we do not agree that its assembly around an unchanged active ingredient meets the requirements of a substantial transformation. The product, Sumatriptan DosePro, remains Sumatriptan in a measured dose ready for needleless injection. Measured dosing has not been held to substantially transform pharmaceuticals except in a case where the actual pharmaceutical changed its character.
You request that in the event CBP does not deem the UK as the country of origin of the product for purposes of 19 USC 1304, Zogenix be permitted to enter and mark the article as “sumatriptan DosePro filled in United Kingdom, Active Ingredient Made in India.” Congressional intent in enacting 19 U.S.C. 1304 was "that the ultimate purchaser should be able to know by an inspection of the marking on the imported goods the country of which the goods is the product. The evident purpose is to mark the goods so that at the time of purchase the ultimate purchaser may, by knowing
where the goods were produced, be able to buy or refuse to buy them, if such marking should influence his will." United States v. Friedlaender & Co. Inc., 27 CCPA 297, 302, C.A.D. 104 (1940). Part 134, Customs Regulations (19 CFR Part 134), implements the country of origin marking requirements and exceptions of 19 U.S.C. 1304. Section 134.43(e), provides that:
Where an article is produced as a result of an assembly operation and the country of origin of such article is determined under this chapter to be the country in which the article was finally assembled, such article may be marked, as appropriate, in a manner such as the following: (1) Assembled in (country of final assembly); (2) Assembled in (country of final assembly) from components of (name of country or countries of origin of all components); or (3) Made in, or product of, (country of final assembly).
As a result of 19 CFR 134.43(e), the terms “Made in," "Product of," and "Assembled in" are words of similar meaning. Accordingly, Customs stated that it will no longer be acceptable to use “Made," "Product of,” or words of similar meaning, along with the words " Assembled in" in a single country of origin marking statement on articles of foreign origin imported into the U.S. See 61 FR 37678, 37679 (1996).
While we have not found a ruling on using the words “filled in”, we believe the situation is analogous to the language “assembled in.” Moreover, the term “filled in” has the same propensity to confuse the ultimate purchaser as to the origin of the goods. The pharmaceutical remains unchanged even after the assembly of the injection device and it determines the country of origin of the goods.
HOLDING:
Sumatriptan from India does not undergo a substantial transformation in the UK when assembled with the DosePro needleless injection unit and must be marked as a product of India in accordance with 19 U.S.C. 1304.
Sincerely,
Myles B. Harmon, Director
Commercial and Trade Facilitation Division