| Public Health Service Food and Drug Administration |
Florida District |
Department of Health and Human ServicesVIA HAND-DELIVERY
WARNING LETTER
FLA-11-36
August 18, 2011
Victor M. Ramirez
Miramar Cosmetics, Inc.
1813 NW 79th Ave.
Doral, Florida 33126
Dear Mr. Ramirez:
During our February 4-14, 2011 inspection of your pharmaceutical manufacturing facility Miramar Cosmetics, Inc., located at 2194 NW 82nd Ave, Miami, FL an investigator from the Food and Drug Administration (FDA) identified significant violations of Current Good Manufacturing Practices (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your drug product(s) 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, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
In addition, your Over-the-Counter (OTC) drug products are manufactured without an approved application. As described below, these drugs are unapproved new drugs and by introducing them into interstate commerce, you are in violation of sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)]. These unapproved new drugs are misbranded pursuant to section 502(c), (e) and (o) of the Act [21 U.S.C. §§ 352(c), (e), and (o)].
We acknowledge your firm’s written response, received April 13, 2011; however, because this response was received more than 15 business days after the Form FDA 483 was issued, it has not been considered1. We plan to evaluate this response along with any other written material provided, as a direct response to this Warning Letter.
Specific violations observed during the inspection include, but are not limited to, the following:
CGMP Violations:
1. Your firm has not established appropriate written procedures to prevent objectionable microorganisms in drug products not required to be sterile [21 C.F.R § 211.113(a)].
For example, your firm failed to establish appropriate written procedures for monitoring the microbiological quality of the water used to manufacture drug products.
This is a repeat observation from the 2007 inspection.
2. Your firm has not established specifications, test procedures, and laboratory control mechanisms [21 C.F.R § 211.160(a)].
For example, your firm has not established the effectiveness of the preservative Isothiazolinone at (b)(4) % used in the “Sport Cream formulation,” a pain relief topical drug product.
This is a repeat observation from the 2007 inspection.
3. Your firm has failed to perform appropriate laboratory testing, as necessary, of each batch of drug product required to be free of objectionable microorganisms [21 C.F.R § 211.165(b)].
For example, your firm failed to conduct microbiological testing for 32 batches of topical drug products (Sport Cream, Hongotrim Spray and Hongotrim Soap) prior to release.
This is a repeat observation from the 2007 inspection.
4. Your firm has failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product [21 C.F.R. § 211.188].
For example, your firm failed to prepare batch records with complete manufacturing instructions. Specifically, the batch records for Hongotrim Spray (lot 100913-1) failed to include: (1) instructions for the addition of ingredients; (2) a statement of actual yield and percentage of theoretical yield at the appropriate phase of processing, and; (3) a record of filling, packaging, and labeling operations.
This is a repeat observation from the 2007 inspection.
Repeat observations from prior inspections indicate that your quality control unit is not exercising its responsibilities or may not have the appropriate authority to carry out its responsibilities. Due to continuing CGMP issues at your firm, we recommend you engage a third party consultant having appropriate CGMP expertise to assess your firm’s facility, procedures, processes, and systems to ensure that your drug products have their appropriate identity, strength, quality, and purity. You are responsible for ensuring that your firm’s drug manufacturing operations comply with applicable requirements, including the CGMP regulations and the Act.
Your firm claims that you are “not manufacturing OTC drugs” at this time. However, we note that you continue to have drugs on the market and still produce products with drug claims. In addition, your firm makes cosmetics, which are also subject to CGMP.
Unapproved and Misbranded OTC Drugs:
Your firm contract manufactures OTC drug products. During the FDA inspection conducted in February, 2011, the FDA investigator obtained labeling for your OTC skin protectant, external analgesic, and fat reduction products. As described in detail below, some of your products are subject to – but fail to comply with – final monographs established under the OTC Drug Review. Other products that you manufacture are not eligible for inclusion in the OTC Drug Review because we are not aware of any evidence that these products, as formulated and labeled, were marketed in the United States at the inception of the OTC Drug Review. As presently labeled and promoted, these products are unapproved and/or misbranded drugs in violation of sections 505(a) and 502 of the Act, [21 U.S.C. §§ 355 and 352] as described below:
HONGOTRIM LIQUID SOAP
The label for HONGOTRIM LIQUID SOAP includes the following claims and statement of ingredients:
• “Relieves itching and burning. For bad odor, cracks and splits.” “INACTIVE INGREDIENTS . . . Water, Cocamidopropyl Betaine, Cocamide Dea, Color, Melaleuca alternifolia (Tea tree oil), Propylene Glycol, Fragrance . . . .”
Drug products, such as HONGOTRIM LIQUID SOAP, that are intended for topical administration for indications related to itching and burning, cracks and splits, are covered under the OTC Final Monograph (FM) for Skin Protectant Drug Products (21 C.F.R. Part 347). However, your product label is inconsistent with the labeling requirements under this FM and violates various provisions of the Act. HONGOTRIM LIQUID SOAP is neither formulated nor labeled in conformance with this FM. Therefore, HONGOTRIM LIQUID SOAP is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)]. The marketing of this product without an FDA-approved application violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)]. Furthermore, this product is misbranded under sections 502(f)(1) of the Act, [21 U.S.C. § 352(f)(1)], because it does not bear the indications, directions and warnings required by the applicable final monograph. (21 C.F.R. §§ 347.50 and/or 347.60).
HONGOTRIM LIQUID SOAP is misbranded under section 502(c) of the Act, [21 U.S.C. § 352(c)] because the product does not contain the required labeling information in an OTC Drug Facts Panel in accordance with 21 C.F.R. § 201.66. For instance, your product’s labeling lacks a “Drug Facts” panel. Additionally, HONGOTRIM LIQUID SOAP is misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to list an active ingredient.
HONGOTRIM SPRAY
The label for HONGOTRIM SPRAY includes the following claims (translated from Spanish) and statement of ingredients:
• “Eliminates itching, bad odor, cracked skin, and peeling of feet and prevents infection . . . .”
• “Ingredients . . . Water, Isopropyl Alcohol, Melaleuca Alternifolia (Tea tree oil), Menthol 0.009%, Propylene Glycol, Fragrance . . . .”
Drug products, such as HONGOTRIM LIQUID SOAP, that are intended for topical administration for indications related to itching and burning, cracks and splits, are covered under the OTC Final Monograph (FM) for Skin Protectant Drug Products (21 C.F.R. Part 347). However, your product label is inconsistent with the labeling requirements under this FM and violates various provisions of the Act. HONGOTRIM SPRAY is neither formulated nor labeled in conformance with this FM. Therefore, HONGOTRIM SPRAY is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)]. The marketing of this product without an FDA-approved application violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)]. Furthermore, this product is misbranded under sections 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] because it does not bear the indications, directions and warnings required by the applicable final monograph. (21 C.F.R. §§ 347.50 and/or 347.60)
HONGOTRIM SPRAY is misbranded under section 502(c) of the Act, [21 U.S.C. § 352(c)] because the product does not contain the required labeling information in an OTC Drug Facts Panel in accordance with 21 C.F.R. § 201.66. For instance, your product’s labeling lacks a “Drug Facts” panel. HONGOTRIM SPRAY is also misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to distinguish between its active and inactive ingredients.
Additionally, HONGOTRIM SPRAY is misbranded under 502(c) of the Act [21 U.S.C. § 352(c)] because the package labeling is inconsistent in that some text appears in Spanish, but the text does not consistently appear in English followed by a Spanish translation. Under 21 CFR §§ 201.15(c)(1), (2), and (3): “All words, statements, and other information required by or under authority of the act to appear on the label or labeling shall appear thereon in the English language: Provided, however, That in the case of articles distributed solely in the Commonwealth of Puerto Rico or in a Territory where the predominant language is one other than English, the predominant language may be substituted for English.” Since your drug products are not solely distributed in Puerto Rico or other Territory, your product labeling needs to appear in English which can then be followed by a Spanish translation and needs to remain consistent throughout. (21 C.F.R. § 201.15(c))
ARTHRI SOLUTION CREAM
The label for ARTHRI SOLUTION CREAM includes the following claims and statement of ingredients:
• “Immediate Muscle, Joint & Arthritis Pain Relief”
• “Temporarily relieves minor pain associated with: . . . arthritis . . . muscle strains . . . simple backache . . . muscle sprains . . . bursitis . . . bruises . . . tendonitis . . . cramps . . . .”
• “Ingredients . . . Aqua, Stearic acid, glyceryl Monostearate, Mineral Oil, Menthol, Methyl Salicylate, MSM, Chondroitin Sulfate, Isothiazolinone . . . .”
Drug products, such as ARTHRI SOLUTION CREAM, intended for indications related to pain relief are being evaluated under the TFM for OTC External Analgesics. The TFM, published in the Federal Register on February 8, 1983 (48 FR 5852), did not include “bursitis” and “tendonitis” as allowable indications and we are not aware of any OTC product formulated and labeled like ARTHRI SOLUTION CREAM having been available in the United States market at the inception of the OTC Drug Review. Accordingly, ARTHRI SOLUTION CREAM is a new drug as defined by section 201 (p) of the Act [21 U.S.C. § 321(p)]. Since ARTHRI SOLUTION 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)].
ARTHRI SOLUTION CREAM is misbranded under section 502(c) of the Act, [21 U.S.C. § 352(c)] because the product does not contain the required labeling information in an OTC Drug Facts Panel in accordance with 21 C.F.R. § 201.66. For instance, your product’s labeling lacks a “Drug Facts” panel. ARTHRI SOLUTION CREAM is also misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to distinguish between its active and inactive ingredients.
ARTHRI SOLUTION CREAM is also misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to distinguish between its active and inactive ingredients.
ARTHRI Life CREAM
The label for ARTHRI Life CREAM includes the following claims and statement of ingredients:
• “ADVANCED ARTHRITIS SOLUTION . . . .”
• “Immediate Muscle, Joint & Arthritis Pain Relief . . . .”
• “Temporarily relieves minor pain associated with: . . . arthritis . . . muscle strains . . . simple backache . . . muscle sprains . . . .”
• “Ingredients: . . . Water, Stearic acid, Glyceryl Monostearate, Mineral Oil, Menthol, Methyl Salicylate, MSM, Chondroitin Sulfate, Isothiazolinone . . . .”
Under 21 C.F.R. § 201.66(b)(2) any component in a drug that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man would be considered an active ingredient. Based on this definition, and because the labeling for ARTHRI Life CREAM does not differentiate the active from the inactive ingredients, it is our position that the components listed above as “Ingredients” for ARTHRI Life CREAM are active ingredients. Because we are not aware of any evidence that a product so formulated and labeled was marketed in the United States at the inception of the OTC Drug Review, ARTHRI Life CREAM is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)] and may not be legally marketed in the United States without an approved application under section 505(a) of the Act [21 U.S.C. § 355(a)].
ARTHRI Life CREAM is also misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to distinguish between its active and inactive ingredients.
Yesoterapia Reductor Cream
The label for Yesoterapia Reductor Cream includes the following claims:
• “#1 Fat Reduction Cream . . . .”
• “Yesoterapia Reductor Cream enhances the natural process of losing weight at the convenience of your lifestyle . . . It is the ultimate solution to trim down the volume of fat from abdomen . . . .”
The indications for use for Yesoterapia Reductor Cream, including the above claims, are not described in any of the rulemakings being considered under the OTC Drug Review. As such, Yesoterapia Reductor Cream does not qualify for evaluation under the ongoing OTC Drug Review. Because we are not aware of any evidence that a product so formulated and labeled was marketed in the United States at the inception of the OTC Drug Review, Yesoterapia Reductor Cream is a “new drug” under section 201(p) of the Act [21 U.S.C. § 321(p)] and may not be legally marketed in the United States without an approved application under section 505(a) of the Act, [21 U.S.C. § 355(a)].
Yesoterapia Reductor Cream is also misbranded under section 502(e)(1)(A)(ii) of the Act, [21 U.S.C. § 352(e)(1)(A)(ii)] because its label fails to distinguish between its active and inactive ingredients.
Lastly, HONGOTRIM LIQUID SOAP, HONGOTRIM SPRAY, ARTHRI SOLUTION CREAM, ARTHRI Life CREAM, and Yesoterapia Reductor Cream are further misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because they were neither manufactured, prepared, propagated, compounded or processed in an establishment duly registered under section 510 of the Act [21 U.S.C. § 360], nor were they included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)].
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 and the occurrence of other violations. It is your responsibility to assure compliance 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. Additionally, FDA may withhold approval of requests for export certificates, or approval of pending drug applications listing your facility, until the above violations are corrected. FDA may re-inspect to verify corrective actions have been completed.
The FDA has identified numerous repeat observations at each of the three inspections. Regardless of the therapeutic category of your products and firm size, you must correct these violations and comply with CGMP requirements and emphasize that failure to do so may result in further legal action. Because of your failure to correct these repeat violations, we also recommend that you engage a third party consultant having appropriate CGMP expertise to assess your firm’s facility. Further, we request that you submit quarterly reports of sufficient detail to the FDA so that we can assess your progress as your firm corrects these violations and ensures that corrective actions are implemented globally.
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. Include an explanation of each step being taken to prevent the recurrence of violations and copies of supporting documentation. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the date by which you will have completed the correction. We also request that you outline the action you are taking to discontinue the marketing of the unapproved drug products at your facility, or any other applicable drug which you may market. Additionally, your response should state if you no longer manufacture or distribute products, and provide the date(s) and reason(s) you ceased production. Please note that if you are no longer marketing this (these) product(s), you must update the Drug Listing files in accordance with 21 C.F.R. § 207.30(a)(2).
Your reply should be sent to the attention of Andrea H. Norwood, Compliance Officer, at the following address: Food and Drug Administration 555 Winderley Place, Suite 200, Maitland, Florida, 32751. If you have questions regarding any issues in this letter, please contact Ms. Norwood at (407) 475-4724.
Sincerely,
/s/
Elizabeth W. Ormond
Acting Director, Florida District
1 Review of Post-Inspection Responses, 74 Fed. Reg. 40211 (Aug. 11, 2009).
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