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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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Enforcement Actions

Iren Corporation 03-Apr-07

Department of Health and Human Services

PHILADELPHIA DISTRICT

900 U.S. Customhouse
2nd and Chestnut Streets
Philadelphia, PA 19106
Telephone: 215-597-4390


WARNING LETTER
07-PHI-03

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

April 3, 2007

Irina Filippova, Ph.D.
President
Iren Corporation
Route 171
RR2 Box 27B5
Union Dale, PA 18470

Dear Dr. Filippova:

An inspection of your drug manufacturing facility located at Route 171, RR2 Box 27B5, Union Dale, PA, conducted by Food and Drug Administration (FDA) investigators on July 18-August 2, 2006, revealed significant deviations from Current Good Manufacturing Practice (CGMP) regulations, Title 21 Code of Federal Regulations, Parts 210 and 211 (21 CFR 210 and 211). These CGMP deviations were listed on an Inspectional Observations (FDA-483) form issued to you at the close of the inspection.

These CGMP deviations cause your human drug products to be adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 351(a)(2) (B)], in that the methods used in, or the facilities or controls used for, the manufacture, processing, packing, and holding of drugs do not conform with CGMP to assure that such drugs meet the requirements of the Act as to safety; and have the identity and strength, and meet the quality and purity characteristics, which they purport or are represented to possess. Our investigators found the following significant deviations from CGMPs for drug products:

1. Failure to verify the identity of each component of a drug product, as required by 21 C.F.R. § 211.84(d)(1). Components used in all drug products are not tested for identity. For example, the active ingredient Sulfur USP, used in Derma 50 Wound Care Cream, batch [redacted] was not tested.

2. Failure to establish appropriate written procedures designed-to prevent objectionable microorganisms in drug products not required to be sterile, as required by 21 C.F.R. § 211.113(a). The firm has not conducted preservative, effectiveness testing on finished products, including Anti-Fungus Cream.

3. Failure to perform appropriate laboratory determination of satisfactory conformance to the final specifications for the drug product, including the identity and strength of each active ingredient, prior to release of drug products, as required by 21 C.F.R. § 211.165(a). The firm does not conduct laboratory testing to determine conformance to established final specifications for all drug products. For example, Topical Ibuprofen Pain Relieving Cream, batch [redacted] and Derma 50 Wound Care Cream, batch [redacted] were not tested prior to distribution.

4. Failure to test in-process materials for identity, strength, quality, and purity and failure to approve or reject in-process materials by the quality control unit during production process as required by 21 C.F.R. § 211.110(c). The firm does not conduct in-process testing on drug products during production. For example, in-process materials in Topical Ibuprofen Pain Relieving Cream, batch [redacted] and Derma 50 Wound Care Cream, batch [redacted] were not tested.

5. Failure to establish a written testing program designed to assess the stability characteristics of drug products, as required by 21 C.F.R. § 211.166(a). For example, the firm does not have a written stability program for Topical Ibuprofen Pain Relieving Cream and Derma 50 Wound Care Cream.

6. Failure to have available adequate laboratory facilities for testing and approval or rejection of components, drug product containers, closures, in-process materials, and drug products for the quality control unit, as required by 21 C.F.R. § 211.22(b). The firm does not have an operating laboratory facility or a contract with an outside laboratory facility to conduct testing on any of their drug products, raw materials, containers and closure systems, and in-process materials.

7. Failure to establish a quality control unit, as required by 21 C.F.R. § 211.22(a). The firm does not have a quality control unit to approve or reject components, drug product container closure systems, in-process test results, packaging/labeling materials, and drug products.

8. Failure to retain an appropriately identified reserve sample that is representative of each lot in each shipment of finished drug product, as required by 21 C.F.R. § 211.170(b). For example, no reserve samples were maintained for Topical Ibuprofen Pain Relieving Cream, batch [redacted] and Derma 50 Wound Care Cream, batch [redacted]

9. Failure to establish written procedures describing the handling of written and oral complaints related to drug products, as required by 21 C.F.R. § 211.198(a). The firm does not have a written complaint procedure.

10. Failure to keep written records and to evaluate, at least annually, the quality standards of each drug product to determine the need for changes in drug product specifications or manufacturing or control procedures, as required by 21 C.F.R. § 211.180(e).

Your website, www.skinnaturalproducts.com, bears claims that cause the following products to be drugs under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(g)(1)(B), because they are intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because they are intended to affect the structure or any function of the body of man:

Iren's Secret Anti-Aging Cream
Website:
"Active Ingredients:
Natural Progesterone USP [derived from Mexican Wild Yam (Dioscorea Villosa) Root)] (1.7%)
Natural Phytoestrogen [derived from Black Cohosh (Cimicifuga Racemosa)] (0.5%)."

"The Natural Alternative to Oral Hormone Therapy . . . ."
" . . . providing transdermal delivery of microencapsulated biological active ingredients thought(sic) the skin . . . ."
"• Depression and other emotional problems have [sic] considered more common in during menopause. Common problems associated with menopause include: (i) changes in the vaginal lining that produce dryness, burning, itching, and pain during sexual intercourse, (ii) hot flashes, night sweats, anxiety, loss concentration, insomnia, feeling of bloating, headaches, heart palpitations, urinary incontinence, itching, and (iii) osteoporosis, as result [sic] a thinning of the bone associated with an increased risk fracture. These problems, that are caused by hormonal deficiencies or imbalances, are efficiency [sic] controlled or prevented by estrogen-replacement therapy . . . ."
"• Women in menopausal period suffer to [sic] risk of heart disease . . . ."
"• Natural Anti-Aging Cream for Menopausal Women (NAACMW) is a therapeutic, deep-penetration cream having bi-directional approach: (i) Reduces discomfort associated with menopausal symptoms by normolzed(sic) imbalance of progesterone and estrogen in the women body due to penetration of natural progesterone and estrogens in the bloodstream through the skin . . . "

Over-the-Counter (OTC) topical hormone containing products labeled, represented or promoted for use as drugs are subject 21 CFR § 310.530(b). This rule states that any OTC drug product, other than hydrocortisone, that is labeled, represented, or promoted as a topically applied hormone-containing product for drug use is regarded as a new drug. The claims described above for Iren's Secret Anti-Aging Cream, a topical hormone-containing product, are evidence of its intended use as a drug. Moreover, OTC topipal hormone creams are new drugs as defined in section 201(p) of the Act, 21 U.S.C. § 321(p), because there is no evidence that they are generally recognized by qualified scientific experts as safe and effective for their labeled uses. Since Iren's Secret Anti-Aging Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 2 U.S.C. § 355(a).

Iren's Secret Anti-Fungus Cream
Website:

"Active Ingredients Purpose
Sulfur USP (in microencapsulated form) (10%)
. . . . . . .Anti-Fungus . . . ."
". . . providing transdermal delivery of microencapsulated biological active ingredients thought (sic) the skin . . . ."
"A therapeutic, deep-penetrating natural anti-fungus cream is useful for fungus treatment in particular for fingernails and toenails [sic] fungus which have proven to be resistant to treatment. Penetrates pores to relieve of [sic] fungus and prevent the development of new fungus infections . . . ."
"• In many cases, antibiotics and hormone therapy are the only recourse, but with the use of Natural Anti-Fungus Cream positive effects are apparent usually within three days of the start [sic] treatment for disease caused by infection with yeast and fungus, and one to three weeks for nailfungus and/or toefungus disorders . . ."

OTC topical products intended for the treatment of fungal nail infections are subject to 21 CFR § 310.545(a)(22)(iii). This regulation provides that there are no active ingredients recognized for OTC use to treat fungal infections of the scalp or nails. Further, the claims identified above for Iren's Secret Anti-Fungus Cream declare "Sulfur USP . . .10%°" to be the active ingredient and claim that the product is useful for "fungus treatment" and that "positive effects are apparent usually within three days of the start [sic] treatment for disease caused by infection with yeast and fungus . . . ." Iren's Secret Anti-Fungus Cream is also subject to 21 CFR Part 333, Subpart C. Sulfur is not included as an active ingredient for any use under 21 CFR 333.210. As a result, Iren's Secret Anti-Fungus Cream is not generally recognized as safe and effective for the treatment of nail fungus, causing it to be a "new drug" as defined in section 201(p) of the Act, 21 U.S.C. § 321(p). Because Iren's Secret Anti-Fungus Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 2 U.S.C. § 355(a).

Iren's Secret Eczema Cream
Website:
"Active Ingredients Purpose
Salicylic Acid (2%),
Sulfur USP (in microencapsulated form)(5%)
......................

Anti-Inflammation
Anti-Microbial & Anti-Bacterial"

It is useful for the treatment of eczema, clears up redness and allows skin to heal . . ."

  • "reduce irritation, itching, and discomfort of the skin"

  • "stimulate antiviral, antibacterial, and anti-microbial activities, and epidermal proliferate [sic] activity of the skin . . . . "

  • "promote faster healing due to quicker absorption and prolonged duration . . . ."

"Natural Eczema Cream is great as a preventive against eczema. One light application at bedtime will help eliminate bacteria from forming redness and may eliminate future skin problems."

OTC topical products intended for the treatment of eczema are subject to the Final Rule for Skin Protectant Drug Products under 21 CFR Part 347. This regulation lists the acceptable active ingredients and their concentration for products labeled for the treatment of minor cuts, scrapes, burns, chapped skin and lips, poison ivy, poison oak, poison sumac and insect bites. Based on the website claims described above, Iren's Secret Eczema Cream contains salicylic acid 2% and sulfur 5% as the active ingredients. This regulation does not permit either of these ingredients as actives when used for this indication. Further, permitted indications under this regulation do not include the prevention of eczema, one of the claims on your website described above. For these reasons, Iren's Secret Eczema Cream is not generally recognized as safe and effective for the treatment of eczema, and is a new drug within the meaning of 201(p) of the Act, 21 U.S.C. § 321(p). Because Iren's Secret Eczema Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 2 U.S.C. § 355(a).

Iren's Secret Ear Drop Oil
Website:

100% ALL NATURAL INGREDIENTS
"Blackcurrent (Ribes Nigrum) Seed Oil, Borage (Borago offinals) Seed Oil, Safflower Oil, Calendula Officinalis Flower Extract, Camphor, Dog Rose (Rosa Canina) Hips Oil, Grape (Vitis Vinifera) Seed Oil, Hazel Nut (Corylus Avellana) Oil, Kiwi (Actinidia Chinensis) Seed Oil, 5-Hydroxytryptophane (or 5-HTP), MSM (MethylSulfonylMethane), Marticaria (Chamomilla recutitia) Nut Oil, Vitamin A, Vitamin E (d Tocopherol), St. John's Wort (Hypericum perforatum) Extract."
"It is useful for the treatment of ear disorders (itching, irritation, inflammation, and etc.).
Penetrates pores to control ear disorders and helps keep ear clear of new itching, inflammation, and irritation. Helps prevent the development of new ear irritation . . ."
"• Symptoms of ear infections include earache, sharp, dull or throbbing pain, a feeling of fullness in the ear, and fiver (sic). External otitis (or swimmer's ear) affects the outer ear. Middle ear infections (otitis media) is behind-the eardrum, where the small bones of the ear are located. Bacteria or virus get into middle ear space cause inflammation and fluid start to build up, associated with the sensation of pressure. Recurring ear infections are generally an indication that an original infection has been resistant to the prescribed treatment . . . ."
"• In many cases, chemicals, antibiotics and hormone therapy are the only recourse, but with the use of Natural Ear Drop Oil positive effects are apparent usually within one and/or two days of the start [sic] treatment . . . ."

OTC topical products labeled or promoted for use in the ear may only be offered for use as an aid in earwax removal and drying of the ears. These products are subject to 21 CFR Part 344. This rule states that the only ingredients found to be generally recognized as safe and effective by the Agency are 95% isopropyl alcohol in a 5 percent anhydrous glycerin base for theindication of drying water-clogged ears, and carbamide peroxide 6.5 percent in an anhydrous glycerin 5% vehicle for the indication of earwax removal . All other OTC otic drugs for the treatment of ear disorders would be new drugs within the meaning of section 201(p) of the Act, 21 U.S.C. § 321(p). Iren's Secret Ear Drop Oil falls within this rule because it is intended for use in treating ear disorders. Therefore, Iren's Secret Ear Drop Oil is not generally recognized as safe and effective for this indication, causing it to be a "new drug" as defined in section 201(p) of the Act. Because Iren's Secret Ear Drop Oil is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 2 U.S.C. § 355(a).

Iren's Secret Psoriasis Cream
Website:
"Active Ingredients Purpose
Fumaric Acid (7.5%)...............................

Anti-Microbial & Anti-Bacterial
" . . providing transdermal delivery of microencapsulated biological active ingredients thought (sic) the skin . . . ."
"It is useful for the treatment of psoriasis, clears up redness and allows skin to heal .
Penetrates in pores to control psoriasis and helps keep skin clear of new redness . Helps prevent the development of new [sic] a psoriasis symptoms . . . ."

OTC topical products intended for the treatment of psoriasis are subject to the final rule under 21 CFR § 358 Subpart H. This regulation lists the acceptable active ingredients and their concentration for products labeled for the control of dandruff, seborrheic dermatitis, or psoriasis. Based on the website claims described above, Iren's Secret Psoriasis Cream contains fumaric acid 7.5% as the active ingredient. This is not an acceptable active ingredient for this indication. Therefore, Iren's Secret Psoriasis Cream is a new drug within the meaning of 201(p) of the Act, 21 U.S.C. § 321(p). Because Iren's Secret Psoriasis Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 2 U.S.C. § 355(a).

Iren's Secret Rosacea Cream
Website:

"Active Ingredients Purpose
Sulfur USP (in microencapsulated form) (8%) .......
Anti-Microbial & Anti-Bacterial
Azelaic Acid (5%)
............................Anti-Inflammation"
" . . providing transdermal delivery of microencapsulated biological active ingredients thought (sic) the skin . . . ."
"It is useful for the treatment of rosacea, clears up rosacea redness and allows skin to heal. Penetrates in pores to control rosacea and helps keep skin clear of new redness . . .
„ • reduce facial swelling, burning, itching, inflammation, irritation, and discomfort of the skin...."
"• remove visible blood vessels and reduce extensive redness . . . .
"• stimulate antibacterial and antimicrobial activities . . .

We are not aware of any evidence that any products containing the ingredients in Iren's Secret Rosacea Cream were marketed in the United States on or before the date of the inception of the OTC Drug Review for the claims you are making for this product. Accordingly, this product is not covered by the OTC Drug Review. Further, we are not aware of any scientific evidence establishing that Iren's Secret Rosacea Cream is generally recognized among scientific experts as safe and effective for its labeled uses. Therefore, this product is a new drug as defined by section 201(p) of the Act, 21 U.S.C. § 321(p). Since Iren's Secret Rosacea Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 21 U.S.C. § 355(a).

Natural Weight Control Cream
Website:

"100% Natural Ingredients: Garcinia Camboqia (Garcinia Hanburyi), Blackcurrent (Ribes Nigrum) Seed Oil, Borage (Borago officinals) Seed Oil, Virgina Safflower Nut Oil, L-Cysteine, Bladderwrack (Fucus Vesiculosus), Guarana (Paullinia Cupana), Coleus Forskohlii Extract (Foskolin), Hazel (Corylus Avellana) Nut Oil, Chromium Picolinate, Organic Caffeine, Grapefruit Extrac (sic), Marticaria (Chamomilla Recutitia) Nut Oil, Phenylalanine, Thyptophan (sic), Vitaminc (sic) C (Ascorbic Acid in microencapsulated form), Vitamin A (in microencapsulated form), Vitamin B3 (Niacin), Vitamin B6 (Pyridoxene), Vitamin E (da Tocopherol) ...."
"• Composition of Natural Weight Control Cream (NWCC) making up a comprehensive program for the treatment and relief of obesity & overweight problems ...."
"NWCC is the effective alternative to surgery, patch & chemical therapy ...."
"• Break Down Fat In Your Stubbom & Problem Areas ...."
"• Stimulate Effectiveness & Ability to Enhance the Burning of Fat ...
"• Dehydrate Your Fat Cells for Easy Metabolism ...."
"• Effectively breaks down stored fat cells form your problem areas for faster metabolism ...."

We are not aware of any evidence that any products containing the ingredients in Natural Weight Control Cream were marketed in the United States on or before the date of the inception of the OTC Drug Review for the claims you are making for this product. Accordingly, this product is not covered by the OTC Drug Review. Further, we are not aware of any scientific evidence establishing that Natural Weight Control Cream is generally recognized among scientific experts as safe and effective for its labeled uses. Therefore, this product is a new drug as defined by section 201(p) of the Act, 21 U.S.C. § 321(p). Since Natural Weight Control Cream is not the subject of an approved new drug application, its marketing in the United States violates section 505(a) of the Act, 21 U.S.C. § 355(a).

Lastly, FDA's regulations state that a drug may be considered a new drug because of the newness of its dosage form or the method or duration of administration or application suggested in its labeling, 21 CFR § 310.3(h)(5). FDA considers all transdermal drug delivery products for OTC use to be new drugs under section 201(p) of the Act because a transdermal delivery system for a drug is not generally recognized by experts to be safe and effective for any uses, 21 U.S.C. § 321(p), and 21 CFR 310.3(h)(5). Therefore, all of your products which are administered through a transdermal delivery system are new drugs under the Act and its implementing regulations. Since none of your products are the subjects of approved new drug applications, their marketing in the United States violates section 505(a) of the Act, 21 U.S.C. § 355(a).

This letter is not intended to be an all-inclusive review of the products that your firm markets. It is your responsibility to ensure that all products marketed by your firm comply with the Act and its implementing regulations.

We received your August 8, 2006 response to the Form FDA-483, Inspectional Observations. Your response states that you have temporarily discontinued the manufacture of drug products, and you would implement corrective actions before restarting the manufacturing operations. However, our recent review of your web site revealed that you are still marketing various products such as Anti-Fungus Cream, Ear Drop Oil and Pain Relieving Cream, which, for the reasons discussed above, are considered drug products under the Federal Food, Drug, and Cosmetic Act.

The issues and 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, and without limitation, seizure and injunction. Other federal agencies may take this Warning Letter into account when considering the award of contracts. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending new drug applications listing your facility as a manufacturer until the above violations are corrected. A reinspection may be necessary.

Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct the 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. If you no longer manufacture or market any of your drug products, your response should so indicate, including the reasons for, and the date on which, you ceased production.

Your reply should be directed to the Food and Drug Administration, Attention: Rhonda J.Walley, Compliance Officer, at the address noted in the letterhead.

Sincerely,

/S/

Thomas D. Gardine
District Director
Philadelphia District Office