Inspections, Compliance, Enforcement, and Criminal Investigations
FVS Holdings, Inc. dba. Green Valley Drugs 8/30/13
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
August 30, 2013
Scot M. Silber
FVS Holdings, Inc. dba. Green Valley Drugs
1850 Whitney Mesa Dr
Henderson, NV 89014-2091
Dear Mr. Silber:
Between March 11, 2013, and March 15, 2013, U.S. Food and Drug Administration (FDA) investigators conducted an inspection of your facility, Green Valley Drugs, located at 1850 Whitney Mesa Drive in Henderson, Nevada 89014. During the inspection, the investigators noted that you were not receiving valid prescriptions for individually-identified patients for a significant number of drug products you were producing. In addition, the investigators observed serious deficiencies in your practices for producing sterile drug products, which put patients at risk. For example, we observed technicians touching the open neck of sterile vials and the bottom of sterile stoppers with non-sterile gloves and performing hand-stoppering during aseptic filling operations. In addition, staff was observed reaching over uncapped vials containing sterile drug products during filling operations, thus disrupting the unidirectional air protecting the vials and allowing for potential contact of the vial top surfaces with non-sterile gown sleeves. Furthermore, FDA investigators noted that sterilized vials are stored uncovered and unprotected from microbial contamination on a shelf in the cleanroom. These practices place your firm’s aseptically-produced injectable products at considerable risk of microbial contamination. These observations and others were noted on an FDA Form 483 issued on March 15, 2013.
During teleconferences with your firm on April 5 and April 8, 2013, we expressed our concerns about your firm’s poor personnel aseptic practices.
During our April 9, 2013 teleconference, you stated that you would cease sterile drug production and make corrections based on the findings identified in the FDA Form 483 issued on March 15, 2013. You also indicated that you would request an FDA re-inspection after the corrections have been made. We expect that you will notify this office before resuming production of sterile drug products. We have not received a written response to the Form 483 issued March 15, 2013.
We acknowledge the April 11. 2013 voluntary recall of all sterile products compounded, repackaged, and distributed by Green Valley Drugs.
Based on FDA’s March 11-March 15, 2013 inspection, it appears that you are producing drugs that violate the Federal Food, Drug, and Cosmetic Act (FDCA).
A. Compounded Drugs Under the FDCA
The FDCA establishes agency jurisdiction over “new drugs,” including compounded drugs. See Medical Ctr. Pharm. v. Mukasey, 536 F.3d 383, 393-94 (5th Cir. 2008) (“compounded drugs are not exempt from the FDCA's ‘new drug’ definition, § 321(p)”). 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.
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 drug, or diluted dosages for children. As a matter of agency discretion, FDA has historically not taken enforcement action against traditional compounding in recognition of the benefit that it affords patients when FDA‑approved, commercially available drugs are inadequate or unavailable.
In 1997, Congress enacted, as part of the Food and Drug Administration Modernization Act of 1997 (FDAMA), a provision that related to pharmacy compounding, codified in section 503A of the FDCA (21 U.S.C. § 353a). In 2001, the Ninth Circuit Court of Appeals declared this section invalid because it included unconstitutional restrictions on commercial speech and those restrictions could not be severed from the rest of section 503A. Western States Medical Center v. Shalala, 238 F.3d 1090 (9th Cir. 2001). The Supreme Court affirmed the Ninth Circuit ruling that the advertising restrictions violated the First Amendment, but it did not consider whether these restrictions could be severed from the rest of section 503A. Thompson v. Western States Medical Center, 535 U.S. 357 (2002). In 2008, the Fifth Circuit Court of Appeals held that the restrictions on commercial speech could be severed from the rest of 503A and that the remainder of 503A is valid and in force. Medical Ctr., 536 F.3d at 404. Thus, the decisions of the Fifth and Ninth Circuits directly conflict on whether the non-advertising provisions of section 503A are valid and in effect.
Your facility is located within the Ninth Circuit where section 503A is invalid, and where FDA continues to apply the enforcement policy articulated in Compliance Policy Guide section 460.200 [“Pharmacy Compounding”], issued by FDA on May 29, 2002 (see Notice of Availability, 67 Fed. Reg. 39, 409 (June 7, 2002)) (the “CPG”). The CPG identifies a non-exhaustive list of factors that the Agency considers in deciding whether to initiate an enforcement action with respect to compounding.
The CPG recognizes that traditional pharmacy compounding practice involves receipt of valid prescriptions for individually identified patients prior to distribution of a drug. During the FDA inspection, investigators observed that your firm does not receive valid prescriptions for individually-identified patients for a significant number of drug products you produce. Based on this factor alone, your conduct does not qualify for the agency’s exercise of enforcement discretion set forth in the CPG and remains subject to all of the FDCA’s requirements. In addition, we remind you that there are other factors that FDA considers in determining whether to exercise enforcement discretion under the CPG.
B. Violations of the FDCA
The drug products that you manufacture and distribute are unapproved new drugs and misbranded drugs in violation of sections 505(a) and 502(f)(1) [21 U.S.C. §§ 355(a) and 352(f)(1)] of the FDCA, respectively. In addition, your sterile drug products are prepared, packed, or held under insanitary conditions whereby they may have been contaminated with filth, or whereby they may have been rendered injurious to health. As such, all sterile products you manufacture are adulterated within the meaning of section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)] of the FDCA. Furthermore, the manufacture of those drugs is subject to FDA’s Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations (CFR), Parts 210 and 211. FDA investigators observed significant CGMP violations at your facility, causing such drug product(s) to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)].
Unapproved New Drug Products
You do not have any FDA-approved applications on file for the drug products you manufacture and distribute, including Methylprednisolone Acetate 40mg/mL and 80mg/mL. Under sections 301(d) and 505(a) of the FDCA [21 U.S.C. §§ 331(d) and 355(a)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA [21 U.S.C. § 355] is in effect for the drug. Your marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.
Misbranded Drug Products
Additionally, because the drug products you manufacture and distribute are intended for conditions that are not amenable to self-diagnosis and treatment by individuals who are not medical practitioners, adequate directions cannot be written for them so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses, causing them to be misbranded under section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] and they are not exempt from the requirements of section 502(f)(1) of the FDCA (see, e.g., 21 C.F.R. §201.115). The introduction or delivery for introduction into interstate commerce of these products therefore violates sections 301(a) of the FDCA [21 U.S.C. § 331(a)].
Additionally, FDA investigators noted that your sterile drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA [21 U.S.C. § 351(a)(2)(A)]. These conditions include technicians touching the open neck of sterile vials and the bottom of sterile stoppers with non-sterile gloves and performing hand-stoppering during aseptic filling operations. In addition, staff was observed reaching over uncapped vials containing sterile drug products during filling operations, thus disrupting the unidirectional air protecting the vials and allowing for potential contact of the vial top surfaces with non-sterile gown sleeves.
FDA investigators also noted CGMP violations at your facility, causing the drugs you manufacture to be adulterated under section 501(a)(2)(B) of the FDCA [21 U.S.C. § 351(a)(2)(B)]. The violations include, for example:
1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).
2. Your firm failed to adequately design the facility with adequate separation or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.42(b)).
3. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
4. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to product aseptic conditions (21 CFR 211.42(c)(10)(v)).
5. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a))
6. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).
7. Your firm does not have, for each batch of drug product purporting to be sterile and/or pyrogen-free, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product (21 CFR 211.167(a)).
The violations cited in this letter are not intended to be an all-inclusive statement of violations that exist at your facility. 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.
FDA strongly recommends that your management immediately undertake a comprehensive assessment of your manufacturing operations, including facility design, procedures, personnel, processes, materials, and systems. In particular, this review should assess the acceptability of your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise could be useful in conducting this comprehensive evaluation.
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. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. Your written reply should be addressed to:
Lawton W. Lum, Director of Compliance
FDA San Francisco District Office
U.S. Food and Drug Administration
1431 Harbor Bay Parkway
Alameda, CA 94502-7070
If you have questions regarding any issues in this letter, please contact Russell A. Campbell, Compliance Officer at 510-337- 6861.
Kathleen M. Lewis, J.D.
Larry L. Pinson, Executive Secretary
Nevada Board of Pharmacy
431 W. Plumb Ln.
Reno, NV 89509
431 W. Plumb Ln.
Reno, NV 89509
 See CPG at 2 (“FDA recognizes that pharmacists traditionally have extemporaneously compounded and manipulated reasonable quantities of human drugs upon receipt of a valid prescription for an individually-identified patient from a licensed practitioner. This traditional activity is not the subject of this guidance.”) (emphasis added); see also CPG at 3 (stating that FDA will consider enforcement action if the pharmacy compounds “drugs in anticipation of receiving prescriptions, except in very limited quantities in relation to the amounts of drugs compounded after receiving valid prescriptions.”).
 Even if section 503A of the FDCA were valid in the Ninth Circuit, your firm would not qualify for section 503A’s exemptions because those exemptions are available only “if the drug product is compounded for an identified individual patient based on the . . . receipt of a valid prescription order or a notation, approved by the prescribing practitioner, on the prescription order that a compounded product is necessary for the identified patient.” See 21 U.S.C. § 353a(a) (emphasis added).
 The specific products made by your firm are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.