VIA UPS
SIGNATURE REQUIRED
WARNING LETTER
August 30, 2013
Scot M. Silber
President/CEO
FVS Holdings, Inc. dba. Green Valley Drugs
1850 Whitney Mesa Dr
Suite 180
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.[1] 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.[2] 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.[3] 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)].
Adulteration Charges
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)).
C. Conclusion
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.
Sincerely,
/S/
Kathleen M. Lewis, J.D.
District Director
cc:
Larry L. Pinson, Executive Secretary
Nevada Board of Pharmacy
431 W. Plumb Ln.
Reno, NV 89509
431 W. Plumb Ln.
Reno, NV 89509
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