Inspections, Compliance, Enforcement, and Criminal Investigations
Nutraceutical Labs, Inc. 25-Jan-05
Department of Health and Human Services
Public Health Service
Los Angeles District
RETURN RECEIPT REQUESTED
January 25, 2005
John R. Rose
Chairman / Chief Executive Officer
Life-Flo Health Care Products
Nutraceutical Labs, Inc.
11202 N. 24th Avenue
Phoenix, AZ 85029-4745
Dear Mr. Rose:
This letter refers to your firm’s marketing and distribution of the products “life-flo Progesta Care,” “life-flo Andro-Edge Superior Androstenedione Stack,” “AllVia Progensa 10,” “AllVia Progensa 20,” “AllVia Progensa 20 PLUS,” and “AllVia AndroEdge.” An inspection of your firm, by the Food and Drug Administration Phoenix Resident Post, Los Angeles District conducted June 10-17, 2004, documented that you market these products for the treatment, cure, mitigation or prevention of disease. The inspection also revealed violations of current good manufacturing practice (CGMP) regulations.
The following list contains examples of claims for these products as they appear on the product labels, in the product sales catalog and on your websites, www.life-flo.com, www.buylife-flo.com, and www.allviahealth.com, where they are offered for sale. All of the products cited in this letter are topically applied hormone creams.
I. Life-flo Brand products
“life-flo for women Progesta-Care Natural Progesterone PMS and Menopause Solutions . . . contains natural, bio-identical progesterone . . .”
“ProgestaCare is the #1 selling natural progesterone cream trusted by millions of women worldwide.”
". . . helps women reduce the severity of PMS symptoms, lessen the effects of menopause and counter-balance the effects of estrogen dominance. ”
". . . recommended by physicians . . . utilizes USP grade micronized natural progesterone derived from wild yam . . . contains an average of 480mg of natural progesterone per ounce. ”
“ . . . HEALTH CONDITIONS ADDRESSED BY THIS PRODUCT: PMS Irregular Bleeding Menopause Infertility Fibroids Cyclical Headaches”
“Customer Care - FAQ.” “Recent studies have discovered that transdennal delivery (ie: absorbed through the skin) of many supplements - such as progesterone, can achieve a higher absorption rate than ordinary methods. . . When supplements are delivered transdermally, they go directly to the bloodstream - initially bypassing the liver - allowing as much as 90% of the supplements to reach the cells where they are needed. . . . How can men benefit from using progesterone? . . . Supplemental progesterone aids in the treatment of health concerns such as osteoporosis and prostatitis. . . . twenty percent of those affected by osteoporosis are men. Many studies have shown that progesterone treatment helps replace the bone density that has been lost due to osteoporosis. Benign prostatic hypertrophy (BPH) . . . Progesterone treatment has been shown to shrink the prostate, alleviating the painful symptoms of BPH . . . it has extremely effective absorption qualities. . . . in a woman’s body ? Progesterone . . . is promoting bone building, thus reducing the risk of osteoporosis. It also helps keep blood sugar levels and protects against endometrial cancer and breast cancer.”
‘Life-flo has developed a group of all natural products specifically designed for women. , . . address hormone imbalance, vaginal dryness, libido, PMS and menopause . . . More women are seeking natural alternatives to Synthetic Hormone Replacement Therapy (HRT). . . HRT is associated with the following health risks *: . . . breast cancer . . . stroke . . .ovarian cancer rates . . . dementia *Women’s Health Initiative Findings”
“life-flo . . . Andro-Edge Superior Androstenedione Stack with Estro-Block™ Promotes natural testosterone production and helps increase libido and muscle mass*”
“Physicians 1st Choice ”
". . . 25mg. of natural Androstenedione”
“AndroEdge . . . includes ingredients that don’t allow the andro to convert to estrogen, . . , Androstenedione is a steroid hormone . . . HEALTH CONDITIONS ADDRESSED BY THIS PRODUCT: Muscle Mass/Tone Athletic Performance Libido Male Sexual Characteristics . . . Each full press of the pump dispenses the doctor recommended 2.5 mg. of natural androstenedione (an average physiological amount recommended for men by many medical researchers.)”
II. AllVia Brand products
1. Progensa 10
“All Via Progensa 10 Natural Progesterone Cream ”
“Progensa 10™ For Men Superior Natural Progesterone Cream, 3 oz. Commonly recommended by medical professionals for: . . . •Prostate Problems •Regulate Cell Apoptosis . . . 10mg of natural progesterone. Progensa 10 contains an average 240mg per ounce of Natural Progesterone USP grade.”
". . . has extremely effective absorption qualities. ”
". . . PLACE ORDER”
"Progensa 10 for Men l Hormone Precursor l Prostate Disease ”
2. Progensa 20
“AllVia Progensa 20 Natural Progesterone Cream”
“Progensa 20™-For Women Superior Natural Progesterone Cream, 3 oz. Commonly recommended by medical professionals for: •PMS •Irregular Bleeding •Fibroids• Menopause •Infertility Headaches” “Measured Dosage Pump dispenses the doctor-recommended 20 mg of natural progesterone . . . 480mg per ounce of Natural Progesterone USP grade.”
“ has extremely effective absorption qualities. ” "PLACE ORDER”
“Progensa 20 for Women Natural Progesterone Cream . . .• PMS
Irregular Bleeding •Cyclical Headaches • Menopausal Symptoms
Hot Flashes •Weight Gain •infertility”
3. Progensa 20 PLUS
“Progensa 20 PLUS for Women”
“Natural Progesterone cream. Also contains MSM, Burdock Root, . . .Dispenses 20 mg of Natural Progesterone with each pump. •PMS•Menopausal Symptoms •Decreased Libido • Mood Swings •Sleep Disorders •Osteoporosis”
4. Androedge 25
Label (as noted on the AllVia website)
“AllVia ANDROEDGE 25 Natural Androstenedione . . . ”
“ANDROEDGE 25™ Superior Natural Androstenedione Cream, 2 oz. Commonly recommended by medical professionals for: •Poor Libido• Fatigue •Low Testosterone •Decreased Muscle Mass . . . plays a vital role in accelerating tissue growth and tissue repair.”
“ . . . In Women, . . . The benefits of a carefully regulated, low-level program can be increased bone density (to help reverse the effects of osteoporosis)” “PLACE ORDER”
“ANDROEDGE 25 Natural Androstenedione Cream. Dispenses 20 mg with each pump. •Decreased Muscle Mass & Muscle Tone •Decreased Bone Density• Low Energy• Reduced Sex Drive •Suboptimal Athletic Performance”
The products “life-flo Progesta Care, ” “life-flo Andro-Edge Superior Androstenedione Stack, ” “AIlVia Progensa 10,” “AllVia Progensa 20,” “AllVia Progensa 20 PLUS,” and ‘‘AllVia AndroEdge” are “drugs,” as defined by the Federal Food, Drug and Cosmetic Act (Act), 9 201(g), because they are intended to cure, mitigate, treat or prevent disease. Moreover, these products are “new drugs,” as defined by 201(p) of the Act, because there is no evidence that they are generally recognized as safe and effective for their intended uses.
The products listed above are subject to a final regulation codified in Title 21 Code of Federal Regulation (21 CFR), Part 310.530, Over-The-Counter (OTC) Topically applied hormone drug products. This regulation states that any over-the-counter drug product that is labeled, represented, or promoted as a topically applied hormone-containing product for drug use, other than hydrocortisone, . . . is regarded as a new drug.
“Progesterone” and “Androstenedione” appear on the labels of your products and constitute an implied therapeutic or physiological effect on the body in addition to the claims that appear in the product labeling.
These products are not the subject of an approved new drug application, and their marketing in the United States violates 505(a) of the Act. Under 505(a) of the Act, a “new drug” may not be introduced or delivered for introduction into interstate commerce unless an FDA-approved application is in effect for such drug.
Further, the Act defines the term, “dietary supplement” in 201(ff)(2)(A)(i) to mean a product that is “[I]ntended for ingestion . . . ” Topical products cannot be dietary supplements because they are not intended for ingestion, but rather bypass the alimentary canal by direct absorption through the skin. Consequently, a product that is not intended for ingestion cannot meet the definition of a “dietary supplement.” Further, all transdermal drug delivery products are new drugs because of the newness of the dosage form or the method or duration of administration or application suggested in the labeling, 21 CFR Part 310.3.
The June 10-17, 2004, inspection at your manufacturing facility, Nutraceutical Labs, Inc., Phoenix, Arizona, also revealed violations of CGMP) regulations (21 CFR sections 210 and 211), which cause these products to be adulterated within the meaning of 501(a)(2)(B) of the Act. We acknowledge your letter, dated July 12, 2004, outlining corrective actions at this facility. Although some of these corrective actions adequately address the inspectional observations, significant CGMP deficiencies remain. These
CGMP deficiencies include:
Failure to establish laboratory controls including scientifically sound and appropriate specifications and test procedures designed to assure that components and drug products conform to appropriate standards of identity, strength, quality and purity [21 CFR 211.160(b)]. For example, the revised written testing procedures submitted with your July 12, 2004, letter are inadequate in that there are no specifications or specific test procedures established for each drug product. In addition, written test methods for some drug product components are not included or referenced in these written procedures.
Failure to establish a written testing program designed to assess the stability characteristics of drug products, including reliable, meaningful and specific test methods [21 CFR 211.166(a)(3)]. For example, the revised written procedures pertaining to stability testing submitted with your response letter still do not include or reference specific test methods to be used in the stability testing of each drug product. Be advised that any such methodology must be stability indicating.
Failure to establish written procedures for the cleaning and maintenance of equipment used in the manufacture, processing, packing, or holding of a drug product [21 CFR 211.67(b)]. For example, cleaning methods have not been validated.
Failure to establish adequate written procedures outlining the responsibilities of the quality control unit [21 CFR 211.22(d)]. For example, written procedures applicable to the quality control unit submitted with your response letter do not identify all personnel having quality control unit authority. In addition, the relationship of the quality control unit to the management structure in charge of production is not defined.
Failure to establish adequate written procedures for production and process control to assure the identity, strength, quality, and purity of the drug products [21 CFR 211.100(a)]. For example, there is no documentation to show that the revised “Quality Control Manual and Standard Operating Procedures” submitted with your response letter was reviewed and approved by your firm’s quality control unit. The two individuals who signed this document are not identified in these procedures as having quality control unit authority. In addition, the procedures in the above referenced manual have no date of implementation. The section in this manual on Master Production and Control Records is inadequate in that it assumes that such records are lot-specific.
This letter is not intended to be an all-inclusive list of deficiencies at your facility. A form FDA 483 was issued and discussed with you at the conclusion of the inspection. It is your responsibility to ensure adherence to each requirement of the Act and its implementing regulations.
We request that you take prompt action to correct the noted violations. Failure to promptly correct these violations may result in enforcement action being initiated by the Food and Drug Administration without further notice. These actions include, but are not limited to, seizure, injunction, and/or civil penalties.
Please notify this office in writing within fifteen working days of receipt of this letter of the specific steps you have taken to correct the noted violations, including an explanation of each step being taken to identify and prevent the recurrence of similar violations. If corrective action cannot be completed within fifteen working days, state the reason for the delay and the time within which the corrections will be completed.
In addition, we note that the labeling for some of your products states that the products contain androstenedione. The Controlled Substances Act (CSA)(21 U.S.C. 801 et seq.) was recently amended by the Anabolic Steroid Control Act of 2004 (Pub. L. 108-358). This amendment becomes effective on January 20, 2005. Once effective, androstenedione will be considered an anabolic steroid and a controlled substance under Schedule III of the CSA. Controlled substances are subject to the authority of the U.S. Drug Enforcement Administration (DEA), the agency with primary responsibility for the regulation of controlled substances. Manufacturers, distributors, and dispensers of controlled substances are required to register with the DEA and comply with a number of requirements (21 U.S.C. 822). In addition, controlled substances are subject to detailed security requirements, recordkeeping requirements, as well as labeling and packaging regulations (see 21 CFR Parts 1300 -1308). Failure to comply with all of the provisions related to Schedule III substances can lead to significant penalties (21 U.S.C 841 - 864). Please contact the DEA for additional information.
If you have any questions regarding this letter, please contact Mariza M. Jafary, Compliance Officer at 949-608-2977.
Your written reply should be addressed to:
Director, Compliance Branch
Food and Drug Administration
Irvine, CA 92612-2446
Alonza E. Cruse