Department of Health and Human Services Public Health Service

Public Health Service
Food and Drug Administration
Center for Biologics Evaluation and Research
1401 Rockville Pike
Rockville MD 20852-1448

DEC 8 2006

Emalee G. Murphy, Esquire
Kirkpatrick & Lockhart Nicholson Graham, LLP
1601 K Street, N.W.
Washington, DC 20006-1600

Dear Ms. Murphy:

The Food and Drug Administration (FDA) has received and reviewed your letter dated July 11, 2006, representing the response of Envita Natural Medical Centers of America. (Envita) to FDA’s Warning Letter dated June 14, 2006 and, for the reasons discussed below, we conclude that it is not sufficient to address our concerns.

In your letter you state that the manufacture of treated cell cultures, manufactured according to Envita’s Standard Operating Procedure for Establishment of Long-Term [redacted] cultures (SOP for [redacted] Cultures), together with the cells’ subsequent administration to patients for treatment of various illnesses (including numerous cancers), falls under the “practice of medicine”. We disagree. As you acknowledge, “the exemption for the practice of medicine is somewhat narrow.” As you describe this concept, it concerns a physician’s administration of an approved product in a manner not provided for in the product’s approved labeling. Significantly, it does not concern the manufacture of an unapproved product, such as the cellular product at issue here. Such cellular products are subject to regulation as HCT/Ps under 21 CFR Part 1271, which requires establishments to register and list their products with FDA, and to manufacture in accordance with good tissue practices, including applicable donor eligibility requirements. In addition, as cellular products that are more than minimally manipulated, they are subject to IND and premarket application requirements, Indeed, as we explained in our Warning Letter, the treated cell cultures manufactured by Envita meet the definition of both a biological product and a drug, yet they are not currently the subject of an approved biologics license (BLA) or a new drug application (NDA), and there is no investigational new drug application (IND) in effect on their behalf.

FDA takes notice of our statement in the July 11, 2006 letter, that “Envita now recognizes that [redacted] is currently labeled for research use only. Accordingly, Envita will cease all use of [redacted].” However, even without the addition to the cell cultures of the [redacted], for that matter, the [redacted] the cell expansion undertaken by Envita for a period of between eight days to six weeks constitutes more than minimal manipulation as provided for under 21 CFR ยงยง 1271.3(f)(2), 1271.1 0(a)(1), because the relevant characteristics of the cells can be altered by that expansion. As a result, even absent the addition of [redacted], an IND application is required for the cell cultures that you are administering to your patients.

In your letter you also note that [redacted] has been approved for administration to patients to treat metastatic melanoma and metastatic kidney disease. However, Envita does not administer [redacted] directly to patients; instead it administers a different product, namely, cells that have been cultured and expanded with [redacted]. You further note that the ex vivo use of [redacted] has been reported in the scientific literature, and that Envita has developed procedures to ensure the safe development and use of the product. Please note that these tvvo points in no way obviate the requirement for an IND. Such an IND will protect the rights, safety, and welfare of subjects who receive this investigational product and will assure that the investigators are experts qualified by scientific training and experience to investigate the safety and effectiveness of drugs.

In your letter you also state that Envita’s product does “not enter interstate commerce in the context of the physician-patient relationship.” We disagree. For example, several of the product’s components have traveled in interstate commerce, and this is sufficient to satisfy the interstate commerce requirement [see, for instance, Baker v. United States, 932 F. 2d 813 (9th Cir. 1991); United States v. Article of Food ... Coco Rico, Inc., 752 F. 2d 11 (1st Cir. 1985); and United States v. Dianovin Phannaceuticals, Inc., 475 F. 2d 100 (1st Cir. 1973). cert. denied, 414 U.S. 830 (1973)].

Next, in your letter you state that Envita has taken every precaution to insure that the public health has been protected and that any risk involved with the cell cultures has been managed. We disagree. Envita has denied subjects receiving this unproven therapy the mandated protections of the IND regulations, which provide for review by FDA and an institutional review board before the study starts. Furthermore, FDA and a responsible institutional review board have been denied the opportunity to review information about adverse events associated with the administration of the cell cultures, and to consider the adequacy of informed consent documents. Finally, there is no evidence that Envita’s cell cultures are tested for sterility, mycoplasma, or endotoxin.

The comments noted above are not intended to identify all of our concerns with respect to the activities of Envita.

We request that you notify FDA in writing within five days of receiving this letter whether Envita intends to take action to correct the violations identified in our Warning Letter dated June 14, 2006. Examples of appropriate corrective actions include discontinuance of the administration of the cultured cells or submission of an INO application. If Envita fails to correct the violations of the Public Health Service Act and the Federal Food, Drug, and Cosmetic Act they may be subject to regulatory action without further notice including, but not limited to, seizure and/or injunction.

Please send your written response to me:

Mary A. Malarkey
Director
(HFM-600)
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
1401 Rockville Pike, Suite 200N
Rockville, MD 20852-1448