FDA issues Second Warning regarding Compounded Drugs (Brilliant Blue G and Triamcinolone) from Franck's

Certain Compounded Drugs from Franck's: FDA Issues Second Warning to Physicians

• Brilliant Blue G (BBG)
• Triamcinolone

[Posted 04/20/2012]
AUDIENCE: Eye Care, Family Practice, Pharmacy
ISSUE: FDA has received additional reports of fungal endophthalmitis (eye infections) in patients who were given Brilliant Blue G (BBG) during eye surgery since the FDA Warning to Physicians was posted on March 19, 2012. The agency has also recently received reports of eye infections in patients who were given injections of drug products containing triamcinolone during eye surgery.
BACKGROUND: Clinicians in several states reported the adverse events. FDA, CDC, and local and state public health agencies are actively investigating these incidents.
These drugs were supplied by Franck’s Pharmacy in Ocala, Florida. Brilliant Blue G is not an approved drug in the United States. Franck’s has recalled all lots of BBG and one lot of Triamcinolone Acetonide P.F
RECOMMENDATION: The Centers for Disease Control and Prevention (CDC) has advised healthcare personnel to stop use of all sterile triamcinolone-containing products purchased from Franck’s until further information regarding the safety of these products is available.
FDA requests that practitioners report to FDA any cases of suspected fungal or bacterial infections, which have occurred within the last six months, associated with drugs labeled as sterile from Franck’s Pharmacy:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm¹
• Download form² or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[04/20/2012 - Updated Warning³ - FDA]
[03/31/2012 - Press Release⁴ - Franck’s Compounding Lab]

Previous MedWatch Safety Alert

[03/19/2012⁵]

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The United States Food and Drug Administration (FDA) Website has a specific page dealing dealing with Pharmacy Compounding, which can be found here.  As of April 23, 2012, this page contained the following information and links:

Pharmacy Compounding

Pharmacy Compounding News

• FDA Statement on Makena¹ (3/30/2011)
• News for Pharmacy Compounders in Regards to Possible Melamine Contamination of Pharmaceutical Components² (9/28/2009)
• Medical Center Pharmacy v. Mukasey³ (8/14/2008)

Significant Compliance Actions

• 2010
  • FDA News: FDA Issues Warning Letters for Drugs Promoted in Fat Elimination Procedure⁴ (4/7/2010)
    • Pure Med Spa⁵
    • All about you medispa⁶
    • Idinhealth⁷
    • Spa 35⁸
    • Monarch medispa⁹
    • Medical Cosmetic¹⁰
    • Zipmed and Mesoone¹¹
  • Warning Letters
    • VanderVeer Center, 11/18/10, Center for Drug Evaluation and Research (CDER)¹²
    • Med Prep Consulting, 7/9/10, New Jersey District Office¹³
    • J & F International Inc., dba Alexandria Medical Arts Pharmacy & Compounding Laboratory, 4/9/2010, Baltimore District Office¹⁴
      
      
• 2009
  • Warning Letters
    • Hopewell Pharmacy and Compounding Center, 9/28/2009, Center for Drug Evaluation and Research (CDER)¹⁵
• 2008
  • FDA News: FDA Takes Action Against Compounded Menopause Hormone Therapy Drugs¹⁶ (1/9/2008)
    • Panorama Compounding Pharmacy¹⁷
    • Saint John's Medical Plaza Pharmacy¹⁸
    • Murray Avenue Apothecary¹⁹
    • Village Compounding Pharmacy²⁰
    • Pharmacy Compounding Specialties²¹
    • Reed's Compounding Pharmacy²²
    • Pacifica Pharmacy²³
  • Warning Letters
    • Civic Center Pharmacy, 12/16/2008, Los Angeles District Office ²⁴
    • Steven's Pharmacy, 11/12/2008, Los Angeles District Office²⁵
    • Aerosol Science Laboratories Inc., 10/29/2008, Center for Drug Evaluation and Research (CDER)²⁶
    • Newman Inc., (dba Medi-Stat), 6/24/2008, New Orleans District Office²⁷
    • Farmacia La Salud Inc., 3/26/2008 San Juan District Office²⁸
    • Bellevue Pharmacy Solutions, 1/14/2008, Kansas City District Office²⁹
    • American Hormones, Inc., 1/10/2008, New York District Office ³⁰
• 2007
  • Warning Letters
    • Med-South Pharmacy Inc., 9/28/2007, New Orleans District Office³¹
    • PharMEDium Services, LLC, 4/13/2007, Dallas District Office³²
    • ComputeRx/Broncho-Dose, Ltd. 3/21/2007, New England District Office³³
    • Kalchem International, Inc., 1/8/2007, Dallas District Office ³⁴
• 2006
  • FDA News: FDA Warns Five Firms To Stop Compounding Topical Anesthetic Creams³⁵ (12/5/2006)
    • Triangle Compounding Pharmacy³⁶
    • University Pharmacy³⁷
    • Custom Scripts Pharmacy³⁸
    • Hal’s Compounding Pharmacy, Inc.³⁹
    • New England Compounding Center⁴⁰
  • FDA News: FDA Warns Three Pharmacies To Stop Mass-Producing Unapproved Inhalation Drugs⁴¹ (8/10/2006)
    • Rotech Healthcare, Inc.⁴²
    • CCS Medical⁴³
  • Warning Letters
    • Spoonamore Drug Co., Inc., 12/1/2006, Cincinnati District Office ⁴⁴
    • Health Dimensions, Inc., 11/27/2006, Detroit District Office ⁴⁵
    • Pharmacy Creations, 10/31/2006, New Jersey District Office⁴⁶
    • Wedgewood Village Pharmacy, 10/31/2006, New Jersey District Office⁴⁷
    • B. Braun Medical Inc., 3/15/2006, Philadelphia District Office⁴⁸
    • Southern Meds Joint Venture, LLC, 2/15/2006, New Orleans District Office⁴⁹
• 2004
  • FDA News: FDA Warns Against Women Using Unapproved Drug, Domperidone, to Increase Milk Production⁵⁰
  • Warning Letters
    • Axium Healthcare Pharmacy⁵¹
    • Drugs Are Us (dba Hopewell Pharmacy)⁵²
    • Peoples Pharmacy, Inc.⁵³
    • Spectrum Chemicals and Laboratory Products⁵⁴

Pharmacy Compounding Advisory Committee Materials⁵⁵

Compounding Surveys

• Report: 2006 Limited FDA Survey of Compounded Drug Products⁵⁶
• Report: Limited FDA Survey of Compounded Drug Products⁵⁷ (2/13/2003)

FDA Alert 66-66; "APIs That Appear To Be Misbranded Under 502(f)(1) Because They Do Not Meet The Requirements For The Labeling Exemptions In 21 CFR 201.122"

(Note: This import alert represents the Agency's current guidance to FDA field personnel regarding the
manufacturer(s) and/or products(s) at issue. It does not create or confer any rights for or on any person,
and does not operate to bind FDA or the public).

Import Alert # 66-66

Published Date: 04/10/2012

Type: DWPE

Import Alert Name:

"APIs That Appear To Be Misbranded Under 502(f)(1) Because They Do Not Meet The
Requirements For The Labeling Exemptions In 21 CFR 201.122"

Reason for Alert:

OASIS records indicate that a large volume of bulk chemicals which can be used as APIs in human
medicines that require NDAs, ANDAs, or INDs are being offered for entry into the U.S.

NDA Imported APIs labeled for further manufacturing and processing or labeled as chemical
substances are frequently destined for pharmaceutical processors that formulate finished drug
products. These drug substances, consigned to individuals or processors who formulate and
distribute human drugs, may be misbranded under Section 502(f)(1).

AIND Sponsors of investigational new drug applications frequently import from foreign
countries either the dosage form or the API for use in laboratory research or clinical trials.

Some persons importing APIs have found that they could obtain entry of these articles if they
simply supply an NDA or IND number at the point of entry. Districts should be alert to the
possibility that: 1) the NDA or IND number provided does not cover the source of the particular
API or 2) the persons importing the API have no authorization to refer to the particular NDA or
IND number. In the past, the persons importing an API have referred to legitimate numbers to
get their APIs released, but the APIs were not destined for use in the application referenced.

CDER and ORA are in the process of making the Establishment Evaluation System (EES)
available to the field. When available, field offices should utilize EES to search and verify the
status of an API, its manufacturer, whether it has been referenced in a valid NDA or whether
it is the subject of a valid IND. Districts that do not have access to EES should contact
DIOP, 301-443-6553 to verify this status.

(OASIS entry records can be compared to CDER records for NDAs, ANDAs, and IND
exemptions to verify the source and status of an API.)

EXEMPTION UNDER 21 CFR 201.122

API labeling invariably lacks adequate directions for use as required by Section 502(f)(1)
of the Act. However, such drugs may be subject to an exemption under 21 CFR subpart 201.122.
This regulation requires specific labeling on the package when adequate directions for use are
missing, such as "Caution: For manufacturing, processing, or repacking."

However, the exemption under 21 CFR 201.122 will not apply to a substance intended for a
use in the manufacture, processing, or repacking of the API which causes the finished article
to be a new drug, unless:

A. an approved NDA covers the production and delivery of the API to the application holder
by persons named in the application; or

B. if no application is approved with respect to the API, the label statement "Caution: For
manufacturing, processing, or repacking" is immediately supplemented by the words "in the
preparation of a new drug or new animal drug limited by Federal law to investigational use,"
and the delivery is made for use only in the manufacture of such new drug or new animal
drug limited to investigational use as provided in 21 CFR part 312 or part 511.1.

The API/manufacturer combinations listed in Attachment A appear to represent importations
of APIs to be used for the manufacture, processing, or repacking of drugs which the Act
and regulations require to be the subject of an approved NDA or a valid IND. However,
either the person receiving the API or the person importing the API appears not to meet the
statutory and/or regulatory requirements regarding labeling. Further, it appears that the Agency
has never inspected the declared manufacturer's GMPs for that imported API.

Guidance:

Detain without physical examination the APIs from the manufacturers identified in the
Red List to this Import Alert.

Districts may detain without physical examination APIs from the persons identified in the
Red List because it appears that the API is misbranded based on its lack of adequate
directions for use as required by section 502(f)(1) of the Act and its failure to meet the
requirements of the exemption found in 201.122. Persons importing these APIs may obtain
release of the detained articles if these persons can supply evidence establishing that the article is:

1. intended for pharmacy compounding that meets the requirements of section 503A of the
Act, including that the API:

a. is accompanied by a valid certificate of analysis,

b. is manufactured by an establishment registered under section 510 of the Act,

and

c. does not appear on a list of drugs identified in 21 CFR 216.24, that have been withdrawn or
removed from the market for reasons of safety or effectiveness.

2. intended for use in the manufacture, processing, or repacking of an over-the-counter
product or prescription product that does not require an NDA;

or

3. a new animal drug, or intended for use in the manufacture, processing, or repacking of a new
animal drug, subject to an NADA;

and, therefore, the API is not subject to this import alert.

OR

Persons importing APIs may obtain release of the detained articles by supplying evidence
establishing that the article is:

1. intended for use in the manufacture, processing, or repacking of a human drug that is itself
the subject of an approved NDA, and that the API is from the appropriate source; or

2. it is covered by IND requirements at 21 CFR 312.110(a).

For questions or issues concerning science, science policy, sample collection, analysis,
preparation, or analytical methodology, contact the Division of Field Science at (301) 796-6600.

This guidance is not intended to address new animal drugs or investigational new animal drugs addressed
by Import Alert number 68-09. If the imported APIs are intended for use in an NADA or INAD, refer
to Import Alert number 68-09.

If the APIs are intended for the compounding of finished drugs by pharmacies, persons
importing the APIs must comply with the requirements in 503A of the FDCA.

This guidance does not apply to excipients or APIs intended for use in OTC drugs or prescription drugs
that do not require a new drug application.

Product Description:

Active Pharmaceutical Ingredients (APIs)

Charge:

"The article is subject to refusal of admission pursuant to section 801(a)(3) in that it appears to be misbranded in that it lacks adequate directions for its intended use. [Misbranding, Section 502(f)(1)]."

OASIS Charge Code - DIRECTIONS

NOTE: Under 502(f)(1), an API must have labeling that lists adequate directions for its use unless the API is subject to exemptions from labeling found in 201.122.

For a list of firms and their products subject to detention without physical examination (DWPE) under this import aller (a.k.a. Red List), click here and scroll to the bottom of the page.

Gary Osborn and Apothecure are Scheduled to Plead Guilty in Compounding case Charging Misbranded Drug Violations

On April 18, 2012, the United States, Gary D. Osborn and Apothecure filed a plea agreement and factual resume in the Northern District of Texas. Pursuant to the plea agreement, Osborn and Apothecure have agreed to plead guilty to the two-count information, charging violations of  21 U.S.C. Section 331(a), 352(a) and 333(a)(1)--all criminal, class A misdemeanors.   ApothéCure and Gary D. Osborn are admitting that they introduced into interstate commerce a misbranded drug with a false and misleading label.  The defendants face up to a year of imprisonment.  Most likely, the defendants will receive probation and be ordered to pay a fine of $100,000.  The parties, while not agreement on the amount of the fine, have agreed that $100,000 would be a reasonable fine in this case.  Nevertheless, the United States' position is that the maximum fine can be imposed up to $250,000 for each count in the information.  The defendants have also agreed to pay restitution to the victims or community, which is mandatory under federal law.  The rearraignment and entry of the plea of guilty are scheduled for April 24, 2012, at 10:30 a.m.

Makena: Example of Where FDA examined a Compounding Pharmacy

Another example where the United States Food and Drug Administration (FDA) has recently (November 2011) examined compounding pharmacies involves compounded versions of Makena, a newly approved drug for premature births, after the manufacturer provided samples of active pharmaceutical ingredients and finished product vials that failed FDA potency standards. The FDA had previously maintained it would not take enforcement action against pharmacies that compounded Makena “based on a valid prescription for an individually identified patient unless the compounded products are unsafe, of substandard quality, or are not being compounded in accordance with appropriate standards for compounding sterile products” Click here for additional information.