Inspections, Compliance, Enforcement, and Criminal Investigations
Kalchem International, Inc. 08-Jan-07
Department of Health and Human Services
Public Health Service
Rockville, MD 20857
January 8, 2007
RETURN RECEIPT REQUESTED
Mr. Haskell Kohen Tabor, D.Ph., President
Kalchem international, Inc.
224 South Main St.
Lindsay, OK 73052
Dear Mr. Tabor:
It has come to our attention that your firm distributes the API domperidone to pharmacies for compounding.
FDA's position is that the Federal Food, Drug, and Cosmetic Act (FDCA) establishes agency jurisdiction over "new drugs," including compounded drugs. FDA's view that compounded drugs are "new drugs" within the meaning of 21 U.S.C. § 321(p), because they are not "generally recognized, among experts . . . as safe and effective," is supported by substantial judicial authority. See Weinberger v. Hynson, Westcotf & Dunning, 412 U.S. 609, 619, 629-30 (1973) (explaining the definition of "new drug"); Prof'Is & Patients for Customized Care v. Shalala, 56 F.3d 592, 593 n.3 (5th Cir. 1995) (the FDCA does not expressly exempt pharmacies or compounded drugs from its new drug provisions); In the Matter of Establishment Inspection of: Wedgewood Village Pharmacy, 270 F. Supp. 2d 525, 543-44 (D.N.J. 2003), aff'd, Wedgewood Village Pharmacy v. United States, 421 F.3d 263, 269 (3d Cir. 2005) ("The FDCA contains provisions with explicit exemptions from the new drug . . . provisions. Neither pharmacies nor compounded drugs are expressly exempted."). FDA maintains that, because they are "new drugs" under the FDCA, compounded drugs may not be introduced into interstate commerce without FDA approval.
The drugs that pharmacists compound are not FDA-approved and lack an FDA finding of safety and efficacy. However, FDA has long recognized the important public health function served by traditional pharmacy compounding. FDA regards traditional compounding as the extemporaneous combining, mixing, or altering of ingredients by a pharmacist in response to a physician's prescription to create a medication tailored to the specialized needs of an individual patient. See Thompson v. Western States Medical Center, 535 U.S. 357, 360-61 (2002). Traditional compounding typically is used to prepare medications that are not available commercially, such as a drug for a patient who is allergic to an ingredient in a mass-produced product, or diluted dosages for children.
Through the exercise of enforcement discretion, FDA historically has not taken enforcement actions against pharmacies engaged in traditional pharmacy compounding. Rather, FDA has-directed its enforcement resources against establishments whose activities raise the kinds of concerns normally associated with a drug manufacturer and whose compounding practices result in significant violations of the new drug, adulteration, or misbranding provisions of the FDCA.
FDA's current enforcement policy with respect to pharmacy compounding is articulated in Compliance Policy Guide (CPG), section 460.200 ["Pharmacy Compounding"], issued by FDA on May 29, 2002 (see Notice of Availability, 67 Fed. Reg. 39,409 (June 7, 2002)).1 The CPG identifies factors that the Agency considers in deciding whether to initiate enforcement action with respect to compounding. These factors help differentiate the traditional practice of pharmacy compounding from the manufacture of unapproved new drugs. They further address compounding practices that result in significant violations of the new drug, adulteration, or misbranding provisions of the FDCA. These factors include considering whether a firm compounds finished drugs from bulk active ingredients that are not components of FDA-approved drugs, without an FDA sanctioned investigational new drug application (IND). The factors in the CPG are not intended to be exhaustive and other factors may also be appropriate for consideration.
We understand your firm is distributing the bulk API domperidone for use in pharmacy compounding. Domperidone is not an active ingredient in any FDA-approved drug products. FDA does not sanction its use in pharmacy compounding and will not exercise enforcement discretion with respect to compounded products that contain domperidone. Accordingly, we also will not exercise our enforcement discretion with regard to the bulk drug substance.
FDA is concerned with the public health risks associated with the compounding of domperidone. There have been several published reports and case studies of cardiac arrhythmias, cardiac arrest and sudden death in patients receiving an intravenous form of domperidone that has been withdrawn from the market in several countries. FDA has become aware of the use of domperidone by lactating women to increase breast milk production because of its effect on prolactin levels. While domperidone is approved in several other countries for the treatment of gastric stasis and gastroparesis, domperidone is not approved in any country for enhancing breast milk production in lactating women. In several countries where the oral form of domperidone continues to be marketed, labels for the product note that domperidone is excreted in the breast milk of lactating women and recommend that women taking domperidone avoid breast-feeding. Because of this, FDA recommends that breastfeeding women not use domperidone to increase milk production.
The domperidone distributed by your firm to pharmacies for compounding is misbranded within the meaning of section 502(f)(1) of the Act (21 U.S.C. § 352(f).(1)). It does not qualify for the section 502(f)(1) exemption set forth in 21 CFR § 201.115, because it is offered to compound drug products that are new drugs under section 201 (p) of the Act (21 U.S.C § 321(p)) and that lack approved applications under section 505 of the Act (21 U.S.C. § 355).
The above violations are not intended to be an all-inclusive list of deficiencies. You should take prompt action to correct these deviations. Failure to promptly correct these deviations may result in additional regulatory action without further notice. These actions include, but are not limited to, seizure of your products or injunction against you and your firm. Federal agencies are routinely advised of the issuance of warning letters so that they may take this information into account when considering the award of government contracts.
Please notify this office in writing within 15 working days of receipt of this letter of any steps you will take to correct the noted violations, including an explanation of each step being taken to prevent the recurrence of similar violations. If corrective action cannot be completed within 15 working days, please state the reason for the delay and the time frame within which the correction will be completed.
You should address your reply to this letter to the U.S. Food and Drug Administration, 5600 Fishers Lane, HFD-317, Rockville, MD 20857 Attention: Meghan Murphy, Biologist. If you have any further questions, please feel free to contact Ms. Murphy at (301) 827-8962.
Michael M. Levy
Division of New Drugs, Labeling, and Compliance
Center for Drug Evaluation and Research
U.S. Food and Drug Administration
Cc: Kaylyn Tabor
224 South Main St., Suite B
Lindsay, OK 73052
1 Although Section 503A of the FDCA (2) U.S.C. § 353a) addresses pharmacy compounding, this provision was invalidated by the Ninth Circuit's ruling in Western States Medical Center v. Shalala, 238 F.3d 1090 (9't' Cir.2001) that Section 503A included unconstitutional restrictions on commercial speech. And those restrictions could not be severed from the rest of 503A. In Thompson v. Western States Medic ol Center, 535 U.S. 357 (2002), the Supreme Court affirmed the Ninth Circuit ruling that the provisions in question violated the First Amendment.