Other Compliance Action Letter

December 18, 2006

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Steven L. Kagen, MD
100 West Lawrence Street
Appleton, WI 54911-5773

Dear Dr. Kagen:

We are writing to you regarding the Polymerized Ragweed and Polymerized Grass products made and marketed by your firm, including products known as Poly RW, Super Ragweed, Poly Grass, and Super Grass. As you are aware, in October 2005, an investigator from the Food and Drug Administration (FDA) collected information from your clinic regarding these products.

You provided follow-up information in response to FDA's inspection on November 9, 2005. In your response, you stated that "[t]he process of compounding ragweed and grass allergens into larger polymerized molecules has been proven to result in extremely safe and effective allergenic vaccines, which are equivalent to corresponding aqueous pollen extracts, without the associated risks of anaphylaxis." We are aware that you have manufactured polymerized ragweed and polymerized grass allergen vaccines from commercially distributed pollen, and you have administered these products to patients in your clinic. It also appears that you have introduced these products for sale outside of Wisconsin, in at least 24 other states, and have received payment for these products.

We are aware that you have made the following claims regarding the use of Polymerized Ragweed and Polymerized Grass in your article entitled "Superior Safety of Polymerized Allergen Vaccines: Zero Systemic Reactions During 55,000 Injections of Polymerized Ragweed and Grass Vaccines in 500 Allergy Patients":

"Here, we extend these findings and further demonstrate that polymerized ragweed and grass vaccines are exceedingly safe, especially in those patients extremely hypersensitive to allergens naturally present in ragweed and grass pollens: 500 allergy patients received over 55,000 injections of polymerized ragweed and grass allergens with zero systemic responses."
"In addition to confirming the complete safety of polymerized ragweed and grass allergen immunotherapy, several new and interesting findings were discovered in the evaluations of our patients on polymerized allergen immunotherapy."

Based on this information, it appears that your products are drugs as defined by section 201(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321(g)), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. In addition, your products are biological products as defined in section 351(i) of the Public Health Service Act (PHS Act), 42 U.S.C. 262(i), because they are a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine, applicable to the prevention, treatment, or cure of a disease or condition of human beings.

In order to introduce or deliver for introduction a biological product into interstate commerce, a valid biologics license (BLA) must be in effect (42 U.S.C. 262(a)). A BLA is issued only after a showing of safety, purity, and potency for the product's intended use. While in the development stage, biological products may generally be distributed for clinical use in humans only if the sponsor has on file an accepted investigational new drug application (21 U.S.C. 355(i); 21 CFR Part 312). Based on a review of our files, FDA has no information that your products are the subject of an approved BLA or an active IND. Therefore, it appears that your shipments of these product represent violations of the FD&C Act and/or the PHS Act.

This letter is not intended to be an all-inclusive list of the deficiencies that may exist at your facility. It is your responsibility to ensure that all products marketed by your firm are in compliance with the FD&C and PHS Acts and their implementing regulations.

You may submit an IND application to the FDA pursuant to Title 21 CFR Part 312. Information to assist you in submitting an IND application is available at http://www.fda.gov/cber/ind/ind.htm. Questions regarding submission of an IND application and assistance may be directed to the FDA's Center for Biologics Evaluation and Research Office of Communications, Training, and Manufacturers Assistance at (800) 835-4709.

If you have questions regarding this letter, please contact Ms. Maria Anderson in the Division of Case Management at (301) 827-6201.

Sincerely,

/s/

Mary A. Malarkey
Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research