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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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J & F International, Inc. 4/9/10

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Baltimore District Office
6000 Metro Drive, Suite 101
Baltimore, MD 21215
Telephone: (410) 779-5454
FAX: (410) 779-5703

FEI: 3005848804


WARNING LETTER
CMS#74925


April 9, 2010


VIA CERTIFIED MAIL
RETURN RECEIPT REQUESTED


Ms. Farzana Kennedy, Co-Owner
J & F International Inc., dba Alexandria Medical Arts Pharmacy & Compounding Laboratory
315 South Washington Street
Alexandria, VA 22314


Mr. John Ayele, Co-Owner
J & F International Inc., dba Alexandria Medical Arts Pharmacy & Compounding Laboratory
315 South Washington Street
Alexandria, VA 22314


Dear Ms. Kennedy and Mr. Ayele:


On April 7-9, 2009, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, located at 315 South Washington Street, Alexandria, Virginia. During the inspection, our investigators documented serious violations of the Federal Food, Drug, and Cosmetic Act (FDCA).


A. Compounded Drugs under the FDCA and FDA's Regulatory Approach to Compounding


The FDCA establishes agency jurisdiction over "new drugs," including compounded. drugs. Compounded drugs fit within the FDCA's definition of "new drug": "[a]ny drug (except a new animal drug ...) [that] is not generally recognized ... as safe and effective for use under the conditions prescribed, recommended., or suggested in the labeling thereof." 21 U.S.C. § 321 (p)(1). See also Weinberger v. Hynson, Westcott & Dunning, 412 U.S. 609, 619, 629-30 (1973) (explaining the definition of "new drug"). There is substantial judicial authority supporting FDA's position that compounded drugs are not exempt from the new drug definition. See Medical Ctr. Pharm. v. Mukasey, 536 F.3d 383 (5th Cir. 2008) ("compounded drugs are not exempt from the FDCA's 'new drug' definition, § 321(p), nor are they uniformly exempt from the FDCA's 'new drug' requirements, §§ 351(a)(2)(B), 352(f)(1), 355"); Prof'ls & Patients for Customized Care v. Shalala, 56 F.3d 592, 593 n.3 (5th Cir. 1995) ("Although the [FDCA] does not expressly exempt 'pharmacies' or 'compounded drugs' from the new drug ... provisions, the FDA as a matter of policy has not historically brought enforcement actions against pharmacies engaged in traditional compounding."); In the Matter of Establishment Inspection of Wedgewood Village Pharm., 270 F. Supp. 2d 525,543-44 (D.N.J. 2003) ("The FDCA contains provisions with explicit exemptions [from] the new drug ... provisions. Neither pharmacies nor compounded drugs are expressly exempted."), aff'd, Wedgewood Village Pharm. v. United States, 421 F.3d 263, 269 (3d Cir. 2005). The drugs that pharmacists compound are not FDA-approved and lack an FDA finding of safety and efficacy. Because compounded drugs are "new drugs" under the FDCA that are unapproved, the statute generally prohibits their introduction into interstate commerce.


In 1997, Congress added section 503A to the FDCA. Under section 503A, certain human drug products that were compounded by a pharmacist or physician were entitled to limited exemptions from FDCA provisions governing drug adulteration, misbranding, and approval. To qualify for these exemptions, a compounding pharmacy had to satisfy several requirements, including prohibitions against advertising and soliciting orders for compounded drugs. In 1998, seven pharmacies challenged the solicitation and advertising prohibitions in section 503A as an impermissible regulation of commercial speech. The Ninth Circuit held that these provisions were unconstitutional and could not be severed from the rest of section 503A, causing all of section 503A to be invalid. Western States Med. ctr. v. Shalala, 238 F.3d 1090 (9th Cir. 2001). In April 2002, the Supreme Court affirmed the Ninth Circuit's ruling that section 503A's advertising and soliciting restrictions were unconstitutional, but the Court did not rule on the severability of those restrictions. Thompson v. Western States Med. Ctr., 535 U.S. 357 (2002).


In May of 2002, FDA issued a revised compliance policy guide (CPG) on pharmacy compounding, CPG Sec. 460.200 ["Pharmacy Compounding"], which explained how the Agency would address pharmacy compounding following the Supreme Court's decision. The CPG sets forth a non-exhaustive list of factors that FDA considers in determining whether to take enforcement action when the scope and nature of a pharmacy's activities raise the kind of concerns ordinarily associated with drug manufacturing.


In September 2004, ten pharmacies brought suit in the U.S. District Court for the Western District of Texas challenging FDA's authority to regulate compounded drugs and inspect state-licensed pharmacies. Medical Center Pharmacy v. Ashcroft (later changed to Medical Center v. Gonzalez and then Medical Center v. Mukasey). In August 2006, the district court issued a ruling interpreting, among other things, the application of the new drug provisions of the FDCA to compounded drugs. In July 2008, the United States Court of Appeals for the Fifth Circuit issued a ruling in Medical Center Pharmacy v. Mukasey, No. 06-51583. The court rejected the finding by the United States District Court for the Western District of Texas and concluded instead that compounded drugs are "new drugs" and "new animal drugs" within the meaning of the FDCA and therefore are subject to regulation by the FDA. The court also ruled on the severability of advertising prohibitions in section 503A of the FDCA, which were found unconstitutional in a prior Supreme Court decisions The Fifth Circuit found that these prohibitions can be severed from section 503A, leaving the remaining parts of that section valid and effective. The Fifth Circuit's severability ruling conflicts with an earlier decision by the United States Court of Appeals for the Ninth Circuit, which held that the unconstitutional parts of section 503A are not severable and that all of section 503A is therefore void.


B. Factual Background


The April 2009 FDA inspection of your facility revealed, in a Monthly Audit Log dated from 11/01/08-04/06/09, that your firm compounded domperidone products for human patients on numerous occasions. FDA is concerned with the public health risks associated with the compounding of domperidone for human use. 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 marketing in several countries. Among other uses, 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.


Compounding drugs using domperidone is inappropriate under both the CPG and section 503A of the FDCA (21 U.S.C § 353a). Under the CPG on human drug compounding, FDA considers 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). Domperidone is not a component of an FDA approved drug, and FDA would not exercise its enforcement discretion for compounded human drugs containing domperidone. Further, under section 503A (b)(1)(A)(i) of the FDCA (21 U.S.C. § 353a(b)(1)(A)(i)), compounded drugs containing domepridone would not be eligible for the exemptions provided by section 503A of the FDCA (21 U.S.C § 353a) because domperidone is not the subject of an applicable USP or NF monograph, nor is it a component of an FDA-approved drug.


FDA understands that some patients may need domperidone to treat certain gastrointestinal disorders. Physicians who would like to prescribe domperidone for their patients may seek to open an IND through the established procedures. Information regarding obtaining an IND for Domperidone can be found at http://www.fda.gov/Drugs/DrugSafety/lnformationbyDrugClass/ucm073070.htm. It should be noted that the IND is obtained by the prescribing physician and not the pharmacy.


C. Violations of the FDCA


Misbranded and Unapproved New Drugs


The domperidone products compounded by your firm are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)]. They are also new drugs under section 201(p) [21 U.S.C. § 321(p)] of the FDCA because they are not generally recognized by qualified experts as safe and effective for its labeled uses. These products may not be introduced or delivered into interstate commerce under section 505(a) of the FDCA [21 U.S.C. § 355(a)] because no approval of an application filed pursuant to section 505 of the FDCA [21 U.S.C. § 355] is in effect for these products. Their introduction or delivery for introduction into interstate commerce violates section 301(d) of the FDCA [21 U.S.C. § 331(d)].


These products are also misbranded under 502(f)(1) of the Act in that their labeling fails to bear adequate direction for their use. Further, these products are not exempt from this requirement under 21 CFR § 201.115, because they are new drugs within the meaning of section 201(p) of the Act and they lack approved applications filed pursuant to section 505 of the Act. Section 301(a) of the FDCA [21 U.S.C. § 331 (a)] prohibits the introduction or delivery for introduction into interstate commerce of any misbranded drug, and section 301(k) of the FDCA [21 U.S.C. § 331(k)] prohibits any act with respect to a drug if the act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.


D. Conclusion


The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility, and they may not be limited to the above-cited drug products. You are responsible for investigating and determining the causes of the violations identified above and for preventing their recurrence or the occurrence of other violations. It is your responsibility to assure that your firm complies with all requirements of federal law and FDA regulations.


You should take prompt action to correct the violations cited in this letter. Failure to promptly correct these violations may result in legal action without further notice, including, without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts.


Within fifteen working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective action within, fifteen working days, state the reason for the delay and the time within which you will complete the correction.


Please send your reply to the U.S. Food and Drug Administration, Attention: Anne Aberdeen, Compliance Officer, 6000 Metro Drive, Suite 101, Baltimore, MD 21215. If you have questions regarding any issues in this letter, please contact Ms. Aberdeen at (410) 779-5134.


Sincerely,

/S/

Evelyn Bonnin
District Director
Baltimore District


cc:
Cathy M. Reiniers-Day,
Deputy Executive Director
Virginia Board of Pharmacy
9960 Mayland Drive, Suite 300
Henrico, VA 23233-1463