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U.S. Department of Health and Human Services

Inspections, Compliance, Enforcement, and Criminal Investigations

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BENEV Company Inc

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 Los Angeles District
Pacific Region
19701 Fairchild
Irvine, CA 92612-2506
Telephone: 949-608-2900
FAX: 949-608-4415
 

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

W/L 20-10

May 18, 2010
 

Mr. Peter Min, CEO
BENEV Company, Inc.
23263 Madero, Suite A
Mission Viejo, CA 92691-2767
 

Dear Mr. Min:

During our September 21 - 30, 2009, and February 2 - 4, 2010 inspection of your pharmaceutical manufacturing facility, Benev Company, Inc. ("BENEV"), located at 23263 Madero, Suite A, Mission Viejo, California, investigator(s) from the Food and Drug Administration (FDA) identified significant violations of Current Food Manufacturing Practice (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 regulations.
 

We have reviewed your firm's responses dated October 7, November 4, December 31, 2009, and February 8, 2010, and note that they lack sufficient corrective actions. In addition, we acknowledge your October 7, 2009 response stating that you have temporarily ceased manufacturing all Over-the-Counter (OTC) drug products at the Mission Viejo, CA facility. Prior to resuming the manufacture of OTC drug products at this facility, you are required to comply with all CGMP regulations.
 

Specific violations observed during the inspection include, but are not limited, to the following:
 

CGMP:
 

1. Your firm has not thoroughly investigated any unexplained discrepancy or the failure of a batch or any of its components to meet its specifications whether or not the batch has already been distributed [21 C.F.R. § 211.192]. For example,

a. Your quality control unit (QCD) has not conducted out-of-specification (OOS) investigations for products that failed to meet bulk drug specifications (e.g., appearance, pH, and microbial contamination). Specifically, your QCD did not conduct OOS investigations for the OOS bulk drug TD+S Sunscreen. However, you used this inprocess bulk drug product to manufacture TD+S Sunscreen (b)(4). Further, this product was released and distributed.
 

b. In your December 31, 2009 response, you provided a revised Standard Operating Procedure (SOP) #(b)(4), "Out Of Specification (OOS) Procedure." Your response is inadequate because the SOP does not describe the steps that will be taken to investigate OOS results (e.g., laboratory testing procedures, production process review).
 

This is a repeat violation from the inspection conducted in 2006.
 

c. Your QCD reviewed and approved the distribution of a drug product that was manufactured using expired components. You fulfilled an order request from your customer by altering the lot number for expired Salicylic Acid Exfoliator 30%. Although a deviation investigation was conducted, the investigation was not thorough (e.g., identification of other affected lots, root cause detelmination, and corrective and preventive actions).
 

In your December 31, 2009, and February 8, 2010 responses, you state that you have "adjusted the system so that there are inventory controls that must be adhered to that have fail-safe controls built in" (sic). Your response is inadequate because you have neither described the inventory controls nor have you provided any documents to demonstrate that these changes have occurred (e.g., SOPs). In addition, you have not provided any information regarding the investigation of the incident. Although you state that the discrepancy was a "one-time incident," you have not indicated how your firm has reached this conclusion. In addition, you have not addressed the QCD's inadequate review of drug product production and controls. Further, you have not indicated whether you performed a review of other products that may have also been affected.
 

2. Your film failed to follow procedures for the handling of all written and oral complaints regarding a drug product, including specific complaint information or a reason that an investigation was found not to be necessary. [21 C.F.R. § 211.198]. For example,
 

a. You failed to ensure that the Complaint Review Form, required by SOP#(b)(4), "Complaint Handling," was used to document complaints. Significantly, your complaint records lacked: (1) product name; (2) lot number; (3) date of the event; (4) results of investigations; and (5) an evaluation of the seriousness of the complaint.
 

In your December 31, 2009, and February 8, 2010 responses, you state that you have created a new complaint investigation form (Form (b)(4) "Complaint Investigation") and have trained personnel regarding its use. However, your response is inadequate because the revised SOP# (b)(4) and/or the new form do not include provisions for review to determine whether a complaint represents a serious and unexpected adverse drug experience subject to the reporting requirements under 21 C.F.R. §§ 310.305 and 514.80.
 

This is a repeat violation from the inspection conducted in 2006.
 

b. You failed to document the reasons that investigations were not necessary for product complaints attributed to adverse reactions or product quality issues as recorded in your complaint log and product return list.
 

Your revised SOP#(b)(4), "Complaint Handling," states that the complaint information will be investigated and reviewed by your QCU upon receipt. Your revised SOP is inadequate because you do not require the documentation of a reason that an investigation was found unnecessary or the name of the responsible person making that determination.
 

3. Your firm failed to reject any lot of components that did not meet the appropriate written specifications for identity, strength, quality and purity [21 C.F.R. § 211.84(e)].
 

For example, a benzoyl peroxide raw material (lot (b)(4)) failed to meet specifications and was not rejected. The raw material was subsequently used to manufacture Acne Spot Treatment (b)(4)). These lots were released and distributed.
 

In your December 31, 2009, and February 8, 2010 responses, you state that this was a "one time incident." Your response is inadequate because you have not indicated how this conclusion was made or provided any information regarding the investigation of the incident.
 

4. Your firm does not have adequate written procedures for production and process controls designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess [21 C.F.R. § 211.100(a)]. For example, you have not validated the manufacturing processes for the following drug products: Salicylic Acid Exfoliator 30%; Numbscents Topical Analgesic Butter (lidocaine HCl, benzocaine); Polyclear Tretinoin Cream; Skin Smoothing Moisturizer (hydroquinone); Salicylic Cleanser; Pure Titanium Dioxide (sunscreen); and Acne Spot Treatment (benzoyl peroxide). Further, your validation studies titled "Hydroquinone Skin Lightening Formula (Protocol (b)(4)," and "TD+S Sunscreen SPF-30 (Protocol (b)(4)," are inadequate because they do not include raw data,1 and an adequate evaluation of critical quality attributes.
 

Your December 31, 2009, and February 8, 2010 responses are inadequate because they fail to address process validation for the listed drug products.
 

This is a repeat violation from the inspection conducted in 2006.

5. Your firm failed to prepare batch production and control records for each batch of drug product produced that includes an accurate reproduction of the appropriate master production or control record [21 C.F.R. § 211.188(a)] and documentation of weights and measures of components used in the course of processing to demonstrate that each significant step in the manufacture and processing of the batch was accomplished [21 C.F.R. § 211.188(b)(4)]. For example,
 

a. Your TD+S Sunscreen SPF-30 specifications for (b)(4) listed in the batch record are inconsistent with the specifications in the master batch record. Your QCD could not provide a justification for these inconsistencies.
 

In your December 31, 2009, and February 8, 2010 responses, you indicate that batch records have been updated to ensure that they contain all necessary specifications. You also state that you will assess the appropriateness of specifications. However, you have not indicated that you will perform a global review of all drug products to ensure that master production and control records include complete manufacturing and control instructions.
 

b. Your control and batch records (and master production records) do not include the weights or measures of active ingredients and raw materials used in the manufacture of your drug products (e.g., Nutracine Tinted Sunscreen SPF 30 and Skin Smoothing Moisturizer (Hydroquinone)).
 

We acknowledge your response dated December 31, 2009, wherein you state that you have added an (b)(4), column on all manufacturing batch records. Your response is not adequate because the master production and control and batch records with (b)(4), columns were not available during the follow-up inspection dated January 2 - 4, 2010, and were not provided in your February 8, 2010 response.
 

6. Your film does not have an adequate written testing program designed to assess the stability characteristics of drug products in order to determine appropriate storage conditions and expiration dates [21 C.F.R. § 211.166(a)]. For example,
 

a. The analytical methods used in your stability studies are not stability-indicating. Your SOP# (b)(4) "Stability Testing," fails to require analyses that (1) identify degradation products or (2) demonstrate the effect of temperature, humidity, oxidation, and light on the drug products.
 

Your firm established expiration dates for drug products without a scientific rationale. Your real-time stability data for Face Sunblock SPF-25 revealed that 2 out of 3 stability lots (b)(4) did not meet the specification for assay at the 12-month test point. You did not investigate the stability failure. However, your firm approved the product expiration for 1 year. In addition, your firm failed to retain sufficient stability samples to conduct a complete analysis for Face Sunblock SPF-25 (b)(4)

Your December 31, 2009, and February 8, 2010 responses are inadequate because you have not specified the stability-indicating tests that will be performed. Although a revised stability testing SOP was provided, you have not provided evidence of stability chamber validation. Further, as a corrective action, you changed the "shelf life" of SPF-25; however, you did not provide stability testing data to support this change. Stability testing of all marketed lots should be performed to assure that the distributed products have the appropriate expiration dates.
 

This is a repeat violation from the inspection conducted in 2006.
 

7. Your firm has not conducted at least one specific identity test and has not established the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals [21 C.F.R. § 211.84(d)(2)].
 

For example, you accepted reports of analysis from suppliers for components labeled as "Lidocaine USP," "Tretinoin USP," "Titanium Dioxide USP," and "Benzoyl Peroxide USP," without conducting at least one specific identity test. In addition, you have not provided documentation demonstrating that you have established the reliability of the supplier's analysis through appropriate validation of the supplier's test results at appropriate intervals.
 

Your December 31, 2009, and February 8, 2010 responses are inadequate because you have not explained how you will assess the reliability of your supplier's analysis.
 

This is a repeat observation from the inspection conducted in 2006.
 

8. Your film has not established written procedures for cleaning and maintenance of equipment [21 C.F.R. § 211.67(b)].
 

Your cleaning validation was limited to the cleaning process of a plastic 55-gallon drum used in the manufacture of Hydroquinone Skin Lightening Formula. You have not established an adequate rationale, including determining whether this product is the most difficult product to clean. The validation also does not include other equipment used in the manufacture and packing of this product.
 

We acknowledge your December 31, 2009 response that describes your cleaning validation protocols and that cleaning validation will be performed on all equipment used to manufacture OTC products. However, during the follow-up inspection dated January 2 - 4, 2010, your cleaning validation protocols were not available. Further, your February 8, 2010 response provided an incomplete cleaning validation protocol for one piece of equipment. In addition, it was not clear whether cleaning validation will still be performed on other equipment.
 

This is a repeat observation from the inspection conducted in 2006.
 

9. You failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform their assigned functions [21 C.F.R. § 211.25(a)].
 

For example, your "QC/ R&D Chemist" has not been trained to perform specific tasks such as microbial limits testing under USP <61>.
 

We acknowledge your December 31, 2009, and February 8, 2010 responses, wherein you state that you will conduct CGMP and SOP staff training biannually with "real time" updates. During the January 2 - 4, 2010 follow-up inspection, we observed that you have begun training production and laboratory personnel. Your response is inadequate because you have not established completion dates and training programs for current good manufacturing practices and SOPs. In addition, your statement regarding "real time" update training remains unclear.
 

This is a repeat violation from the inspection conducted in 2006.
 

New Drug and Misbranding:

In addition to the CGMP violations, you manufacture and market unapproved new drugs in violation of the Act at your facility in Mission Viejo, CA. Based on the information collected during the inspection, you manufacture the following prescription drugs, including, but not limited to:
 

Polyclear Tretinoin Cream (Tretinoin 0.1%)
Nutracine Skin Lightener PM (Hydroquinone USP 4%)
 

The above products are drugs within the meaning of section 201(g) of the Act, [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases. Further, they are ''new drugs" within the meaning of section 201(P) of the Act [21 U.S.C. § 321(P)] because they are not generally recognized as safe and effective for their labeled uses. Under sections 301(d) and 505(a) ofthe Act [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 either section 505(b) or G) of the Act [21 U.S.C. § 355(b) or (j)] is in effect for the drug. Based on our information, you do not have any FDA approved applications on file for these drug products.
 

Additionally, under section 301(a) of the Act [21 U.S.C. § 331(a)] it is prohibited to introduce into or deliver for introduction into interstate commerce a misbranded drug. The above products are misbranded because, as prescription drugs, 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 use as required under sections 502(f)(1) of the Act [21 U.S.C. § 352(f)(1)] and because they lack required approved applications, they are not exempt from this requirement under 21 C.F.R. § 201.115.
 

The introduction or delivery for introduction into interstate commerce of these products without approved new drug applications violates section 301(a) and (d) of the Act [21 U.S.C. §§ 331(a) and (d)]. Therefore, you should discontinue manufacturing all unapproved drugs at all facilities immediately.
 

You are also in violation of the drug registration and listing requirements because you have not listed the above products as required by section 510(j)(1) of the Act [21 U.S.C. § 360(j)(1)]. Your facility is not exempt from the drug listing requirements in section 510(g) of the Act [21 U.S.C. § 360(g)].
 

Moreover, your firm also manufactures numerous drug products for over-the-counter use. Specifically, the labeling collected during the inspection of your facility, and the labeling on your Internet website, www.benev.com. bear 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. These products are:
 

NumbScents Topical Analgesic Butter
Silicone Spray SS-50| protect
Acne Spot Treatment AST-2 Anti-Bacterial
Professional AcneRx Cream
Salicylic Acid Exfoliator SAE-2 Clarify
Salicylic Cleanser SC-2 Clarify
The Acne Repair Kit which consists of
Acne Spot Treatment AST-2 Anti-Bacterial
Hyaluronic Moisturizer HM-50 hydrate
Salicylic Cleanser SC-2 Clarify
Sulfur Mask SMT-2 clarify
 

OTC drugs that do not require FDA approval through the new drug process are subject to the OTC Drug Review.
 

As described in detail below, "NumbScents Topical Analgesic Butter," "Silicone Spray SS-50 protect" and "Acne Spot Treatment AST-2 Anti-Bacterial" are not eligible for inclusion in the OTC Drug Review because their formulation, labeling or both are not consistent with Tentative Final Monographs proposed by the agency; and we are not aware of any evidence that such products as formulated and labeled were marketed in the United States on or before the inception of the OTC Drug Review.
 

"Salicylic Acid Exfoliator SAE-2 Clarify," "Salicylic Cleanser SC-2 Clarify," the Acne Repair Kit, "Hyaluronic Moisturizer HM-50 hydrate" and the "Sulfur Mask SMT-2 clarify" are subject to - but fail to comply with - the Final Monograph for OTC acne products established under the OTC Drug Review.
 

Therefore, all of these products listed above-with the exception of "Professional AcneRx Cream"-are new drugs, as defined by section 201(P) of the Act (21 U.S.C. § 321(P)); and under sections 301(d) and 505(a) of the Act (21 U.S.C. §§ 331(d) and (355). A new drug may not be introduced or delivered for introduction into interstate commerce unless an FDA-approved application is in effect for it. Since there are no applications for these products, your marketing of them violates sections 301(d) and 505(a) of the Act (21 U.S.C. §§ 331(d) and (355)).

Further, "Salicylic Acid Exfoliator SAE-2 Clarify," "Salicylic Cleanser SC-2 Clarify" and the "Acne Repair Kit" and its components (which includes "Acne Spot Treatment AST-2 AntiBacterial," "Salicylic Cleanser SC-2 Clarify," "Hyaluronic Moisturizer HM-50 hydrate" and "Sulfur Mask SMT-2 clarify") are misbranded under sections 502(f)(1) and (f)(2) of the Act (21 U.S.C. §§ 352(f)(1) and (f)(2)), because they do not bear the indications, directions, and warnings required by the final monograph for OTC acne products.
 

In addition, the labels for your products fail to comply with the regulations under 21 C.F.R. § 201.66 covering the format and content of OTC drug labeling. These regulations establish the criteria for ensuring OTC drug labeling information is conspicuous at the time of purchase and use. See http://www.fda.gov/cder/Offices/OTC/DrugFactsFinalRule.pdf. The failure to comply with these regulations causes your OTC drug products to be misbranded under section 502(c) of the Act. (21 U.S.C. § 352(c)).
 

Your products are also misbranded under section 502(o) of the Act (21 U.S.C. § 352(o)), because they are not listed as required by section 510(j) of the Act (21 U.S.C. § 360(j)). Your facility is not exempted from drug listing requirements under 21 C.F.R. § 207.10 and section 510(g) of the Act (21 U.S.C. § 360(g)), because it is engaged in the manufacture and distribution of drugs. Further, your products are also misbranded under section 502(o) of the Act (21 U.S.C. § 352(0)), in that they were manufactured in an establishment not duly registered under section 510 of the Act (21 U.S.C. § 360). The failure to register or list a drug as required by section 510 is prohibited under section 301 of the Act (21 U.S.C. §331(P).
 

Below is an analysis of the regulatory status of each of your OTC dmg products listed above, which includes excerpts of the violative labeling and the specific new drug and misbranding charges. Note that this is not an all inclusive description of all violative labeling for your OTC drug products.
 

Analysis of Each Product's Regulatory Status

NumbScents Topical Analgesic Butter
Label:
"Active Ingredients:
Benzocaine 19.00%
Lidocaine Hydrochloride 4.00%"
"Other Ingredients:
Shea Butter (butyrosperium parki), Butylparaben, Ethylparaben, Propylparaben,
 

Fragrance"
"For Laser Treatments & Fillers"
 

As stated above, the labeling for this product, including its name "NumbScents Topical Analgesic Butter," bears claims that cause this product to be a drug under section 201(g)(1)(B) of the Federal Food, Drug, arid Cosmetic Act (the Act), 21 U.S.C. § 321(g)(1)(B), because the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Drug products intended for indications such as those promoted for NumbScents Topical Analgesic Butter, namely a topical analgesic, are being evaluated under the developing monograph for OTC External Analgesics within the overall OTC Drug Review. The Tentative Final Monograph (TFM), published in the Federal Register on Febmary 8, 1983, (48 Fed. Reg. 5852), did not include the particular combination of active ingredients in this
product, and therefore this ingredient combination was not evaluated in the developing monograph. Additionally, the indications for use for the NumbScents Topical Analgesic Butter, such as laser treatments and fillers, are not included in the developing monograph for OTC external analgesics or for any other OTC use. Furthermore, we are unaware of this combination of active ingredients and these indications for use having been marketed OTC in the United States at the inception of the OTC Drug Review. Therefore, this product is not deferred to that Review. Moreover, this product has not been recognized by qualified scientific experts as safe and effective for its labeled external analgesic uses. Accordingly, NumbScents Topical Analgesic Butter is a "new drug" as defined by section 201(P) of the Act, 21 U.S.C. § 321(P). Since NumbScents Topical Analgesic Butter is not the subject of an approved new drug application, its marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
 

NumbScents Topical Analgesic Butter is also misbranded under Section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by Section 510(j) of the Act [21 U.S.C. § 360(j)]. The law requires that you file with the Secretary a list of all drugs which are being manufactured for commercial distribution.
 

Silicone Spray SS-50 | protect
Website:

"Ingredients Water (Aqua), Dimethicone, Phenoxyethanol, Methylparaben, Ethylparaben, Propylparaben Butylparaben."
"A fine mist of dimethicone designed to provide a breathable screen against environmental agressors. Great for maintaining hydration of newly revealed post-procedure skin, providing a finish over corrective products and moisturizers, and blending with Pure Titaninm Dioxide for a smooth application."
 

The labeling for this product bears claims such as "breathable screen against environmental aggressors... [and] maintaining hydration of newly revealed post-procedure skin" that cause this product to be a drug under section 201(g)(1)(B), 21 U.S.C. § 321(g)(1)(B) of the Act, because it is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, 21 U.S.C. (g)(1)(C), because it is intended to affect the structure or any function of the body of man.
 

We are unaware of these indications for use having ever been marketed OTC in the United States at the inception of the OTC Drug Review. Therefore, this product is not deferred to that Review. Moreover, this product has not been recognized by qualified scientific experts as safe and effective for its labeled uses. Accordingly, "Silicone Spray SS-50 | protect" is a "new drug" as defined by section 201(P) of the Act, 21 U.S.C. § 321(P). Since "Silicone Spray SS-50 | protect" is not the subject of an approved new dtug application, its marketing in the United States violates section 505(a) of the Act, 21 U.S.C. § 355(a).
 

Silicone Spray SS-50 is misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because the product does not bear a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.

Silicone Spray SS-50 is also misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by section 510(j) of the Act [21 U.S.C. § 3600)]. The law requires that you file with the Secretary a list of all drugs which are being manufactured for commercial distribution.
 

Acne Spot Treatment AST-2 Anti-Bacterial
Label:
"Active ingredients: Benzoyl Peroxide 2.0%
Other Ingredients: Butylene Glycol, Butyiparaben, Cyclopentasiloxane, Dimethicone, Ethylparaben, Isohexadecane, Methylparaben, Oligopeptide-10, PEG-4, Phenoxyethanol, Polysilicone-11, Polysorbate 80, Propylparaben, SD Alcohol 40, Sodium Acrylate/ Sodium Acryloyldimethyl Taurate Copolymer, Sodium Hyaluronate, and Water"
Website:
"AST-2 | anti-bacterial" ... "Contains 2.0% benzoyl peroxide to help eliminate existing acne blemishes, promote fast healing, and prevent future breakouts ...."
 

The labeling for "Acne Spot Treatment AST-2 Anti-Bacterial" bears claims that cause this product to be a drug 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 the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Specifically, this product is promoted as an OTC drug for the treatment of acne and it contains benzoyl peroxide as an active ingredient.
 

OTC drug products intended for indications such as those promoted for "Acne Spot Treatment AST-2 Anti-Bacterial" and that contain benzoyl peroxide as an active ingredient have recently been evaluated under the developing monograph for Topical Acne Drug Products within the overall OTC Drug Review.2

The antibacterial uses for the "Acne Spot Treatment AST-2 Anti-Bacterial" are not included in the developing monograph for Topical Acne Drug Products. Furthermore, we are unaware of such a product that includes acne and antibacterial indications for use that were marketed OTC in the United States at the inception of the OTC Drug Review. Therefore, this product is not deferred to that Review. Moreover, this product has not been recognized by qualified scientific experts as safe and effective for its labeled uses. Accordingly, "Acne Spot Treatment AST-2 Anti-Bacterial" is a "new drug" as defined by section 201(p) of the Act, 21 U.S.C. § 321(p). Since "Acne Spot Treatment AST-2 Anti-Bacterial" is not the subject of an approved new drug application, its marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
 

"Acne Spot Treatment AST-2 Anti-Bacterial" is misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because the product does not bear a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.
 

In addition, "Acne Spot Treatment AST-2 Anti-Bacterial" is misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by Section 5100) of the Act [21 U.S.C. § 360(j)]. The law requires that you file with the Secretary a list of all drugs which are being manufactured for commercial distribution.
 

Professional AcneRx Cream
Label:

"Active ingredients: Benzoyl Peroxide 2.0%"
Other Ingredients: Water, Cyclopentasiloxane, Polysilicone-11, Butylene Glycol, Oligopeptide-10, SD Alcohol 40, Sodium Hyaluronate, Peg-4, Sodium Acrylate/Sodium Acryloyldimethyl Taurate Copolymer, Isohexadecane, Polysorbate 80, Phenoxyethanol, Methylparaben, Ethylparaben, Propylparaben and Butylparaben"
 

The labeling for "Professional AcneRx Cream" bears claims that cause this product to be a drug 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 the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Specifically, this product is promoted as an OTC drug for the treatment of acne and it contains benzoyl peroxide as an active ingredient.
 

As an OTC dmg for the treatment of acne, "Professional AcneRx Cream" is misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because the product labeling does not bear a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.
 

In addition, "Professional AcneRx Cream" is misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)]. The law requires that you file with the Secretary a list of all drugs which are being manufactured for commercial distribution.

Salicylic Acid Exfoliator SAE-2 Clarify
Label:

"Active Ingredient: Salicylic Acid 2.0%
Other Ingredients:
Propylene Glycol and SD Alcohol 40"
Website:
"Beta-hydroxy acid with anti-microbial effects superficially exfoliates skin to remove excess cellular buildup. Helps reduce comedones and acne, diminish the appearance of fine lines and wrinkles, and reduces pore size with regular use."
 

The labeling for "Salicylic Acid Exfoliator SAB-2 Clarify" bears claims that cause this product to be a drug under section 201(g)(1)(B) of the Act, 21 U.S.C. § 321(g)(1)(B), because the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Specifically, this product is promoted as an OTC drug for the treatment of acne and therefore, subject to the requirements of the OTC Final Monograph for Topical Acne Drug Products (21 C.F.R. Part 333, Subpart D).
 

However, "Salicylic Acid Exfoliator SAB-2 Clarify" is not labeled in conformance with this final monograph, In particular, the antibacterial uses for the "Salicylic Acid Exfoliator SAB-2 Clarify" are not included as indications for use in the OTC Final Monograph for Topical Acne Drug Products. Therefore, "Salicylic Acid Exfoliator SAE-2 Clarify" 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 approved applications under section 505(a) of the Act [21 U.S.C. § 355(a)]. Since "Salicylic Acid Exfoliator SAB-2 Clarify" is not the subject of an approved new drug application, their marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C, §§ 331(d) and 355(a)].
 

"Salicylic Acid Exfoliator SAE-2 Clarify" is also misbranded under Section 502(c) of the Act [21 U.S.C. § 352(c)] because the product labeling does not bear a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.
 

In addition, "Salicylic Acid Exfoliator SAB-2 Clarify" is misbranded under section 502(o) of the Act [21 U.S.C. § 352(0)] because it is not included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)]. The law requires that you file with the Secretary a list of all drugs which are being manufactured for commercial distribution.

Salicylic Cleanser SC-2 Clarify
Label:
"Active ingredient:
Salicylic Acid 2.0%
Other Ingredients: Acrylates/ C10-30 Alkyl Acrylate Crosspolymer, Aloe Barbadensis Leaf Juice, Ammonium Lauryl Sulfate, Benzyl Alcohol, Butylene Glycol, Chamomilla Recutita (Matricaria) Flower Extract, Cocamidopropyl Betaine, Lauramide DEA, Methylchloroisothiazolinone, Methylisothiazolinone, Sodium C14-16 Olefin Sulfonate, Sodium Laureth Sulfate, Tetrasodium EDTA, Triethanolamine, and Water (Aqua)"
Website:
"Contains 2% salicylic acid, which has been shown to be effective in the control of acne. Salicylic acid acts as an anti-bacterial and anti-microbial for acne conditions but may also improve the appearance of fine lines due to it's exfoliating properties ...."
 

The labeling for "Salicylic Cleanser SC-2 Clarify" bears claims that cause this product to be a drug under section 201(g)(1)(B) of the Act, 21 U.S.C. § 321(g)(1)(B), because the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Specifically, this drug product is promoted as an OTC drug for the treatment of acne and therefore, it is subject to the requirements of the OTC Final Monograph for Topical Acne Dmg Products (21 C.F.R. Part 333, Subpart D).
 

However, "Salicylic Cleanser SC-2 Clarify" is not labeled in conformance with this final monograph. In particular, the antibacterial uses for the "Salicylic Cleanser SC-2 Clarify" are not included as indications for use in the OTC Final Monograph for Topical Acne Drug Products. Therefore, "Salicylic Cleanser SC-2 Clarify" 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 approved applications under section 505(a) of the Act [21 U.S.C. § 355(a)]. Since "Salicylic Cleanser SC2 Clarify" is not the subj ect of an approved new drug application, its marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
 

"Salicylic Cleanser SC-2 Clarify" is also misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because the product labeling does not bear a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.
 

In addition, "Salicylic Cleanser SC-2 Clarify" is misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)]. The law requires that you file with the Secretary a list of all dmgs which are being manufactured for commercial distribution.

Acne Repair Kit

The product labeling for the "Acne Repair Kit" represent the product as an OTC topical acne treatment that consists ofthe following topical products:
 

Salicylic Cleanser SC-2 Clarify
Acne Spot Treatment AST-2 Anti-Bacterial
Hyaluronic Moisturizer HM-50 hydrate
Sulfur Mask SMT-2 clarify
 

The labeling on your Internet website quoted below lists the products within the kit and components contained in these products:
 

http://www.benev.comJproduct_detail.asp?ca_id=11&fl=1&s1=11&p_id=10033
 

"Salicylic Cleanser
Active Ingredient: Salicylic Acid 2.0%. Other Ingredients: Acrylates/ C10-30 Alkyl Acrylate Crosspolymer, Aloe Barbadensis Leaf Juice, Ammonium Lauryl Sulfate, Benzyl Alcohol, Butylene Glycol, Chamomilla Recutita (Matricaria) Flower Extract, Cocamidopropyl Betaine, Lauramide DEA, Methylchloroisothiazolinone, Methylisothiazolinone, Sodium C14-16 Olefin Sulfonate, Sodium Laureth Sulfate, Tetrasodium EDTA, Triethanolamine, Water (Aqua)."

"Acne Spot Treatment Active Ingredient: Benzoyl Peroxide 2.0%. Other Ingredients: Butylene Glycol, ButyIparaben, Cyclopentasiloxane, Dimethicone, Ethylparaben, Isohexadecane, Methylparaben, Oligopeptide-10, PEG-4, Phenoxyethanol, Polysilicone-11, Polysorbate 80, Propylparaben, SD Alcohol 40, Sodium Acrylate/ Sodium Acryloyldimethyl Taurate Copolymer, Sodium Hyaluronate, Water (Aqua)."
 

"Hyaluronic Moisturizer
Water (Aqua), 1,2-Hexanediol, Caprylyl Glycol, Sodium Hyaluronate, Carbomer, Aminomethyl Propanol."
 

"Sulfur Mask
Water (Aqua), Kaolin, Bentonite, Propylene Glycol, Glycerin, Polysorbate 20, Colloidal Sulfur, Melaleuca Altemifolia (Tea Tree) Leaf Oil, Lactic Acid, Eucalyptus Globulus Leaf Oil, Phenoxyethanol, Methylparaben, Ethylparaben, Propylparaben, Butylparaben."
 

The uses of the "Acne Repair Kit" are described in the product name itself and the following statement on the Internet website.
 

"The BENEV Acne Repair Kit is engineered with pharmaceutical-quality active ingredients to treat and help control the causes of acne breakouts and restore optimum health to skin for a smooth, clear, healthy appearance."
 

The kit's directions for use on your Internet website are also quoted below:
 

http://www.benev.com/product_detail.asp?ca_id=11&fl=1&sl=11&p_id=10033&case=u
 

"1. Cleanse skin with BENEV Salicylic Cleanser, avoiding the eye area. Rinse well and gently pat skin dry with a clean towel. Use nightly or as directed by your physician.
 

2. Apply BENEV Sulfur Mask at night on the entire face and/or neck and chest, avoiding the eye area. Remove with a lukewann to cool wet cloth. Use 1-2 times per week or as directed by your physician.
 

3. Apply 1-3 drops of BENEV Hyaluronic Moisturizer to your entire face and neck as needed, morning and evening.
 

4. Apply a small amount of BENEV Acne Spot Treatment to clean, dry skin, directly on affected areas. Use day and night or as directed by your physician."
 

The labeling for the "Acne Repair Kit" bears claims that cause this product to be a drug 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 the product is intended for the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the Act, because the product is intended to affect the structure or any function of the body of man. Specifically, this product is promoted as an OTC drug for the treatment of acne.
 

The acne claims noted above subject the "Acne Repair Kit" to the requirements of the OTC Final Monograph for Topical Acne Drug Products (21 C.F.R. Part 333, Subpart D). The "Acne Repair Kit" is neither formulated nor labeled in conformance with this final monograph. In particular, the kit's directions for use noted above, conveys to the consumer that the "Acne Spot Treatment AST-2 Anti-Bacterial," "Salicylic Cleanser SC-2 Clarify," "Hyaluronic Moisturizer HM-50
hydrate" and the "Sulfur Mask SMT-2 clarify" are to be used in conjunction with each other as a treatment for acne. The OTC Final Monograph for Topical Acne Dmg Products does not allow for such a combination of products as a treatment for acne. Furthermore, the "Acne Repair Kit" contains the two topical treatments for acne, "Salicylic Cleanser SC-2 Clarify" and the "Acne Spot Treatment AST-2 Anti-Bacterial" which are unapproved "new drugs" as explained earlier.
 

Therefore, the "Acne Repair Kit" 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 approved applications under section 505(a) of the Act [21 U.S.C. § 355(a)]. Since the "Acne Repair Kit" is not the subject of an approved new drug application, its marketing in the United States violates sections 301(d) and 505(a) of the Act [21 U.S.C. §§ 331(d) and 355(a)].
 

The "Acne Repair Kit" is also misbranded under section 502(c) of the Act [21 U.S.C. § 352(c)] because the product labeling lacks a "Drug Facts" panel which is required under 21 C.F.R. § 201.66.
 

In addition to the above violations, the "Acne Repair Kit" is misbranded under section 502(o) of the Act [21 U.S.C. § 352(o)] because it is not included in a list required by section 510(j) of the Act [21 U.S.C. § 360(j)]. You must file with the Secretary a list of all dmgs which are being manufactured for commercial distribution.
 

Regulatory Status of Hyaluronic Moisturizer HM-50 hydrate and Sulfur Mask SMT-2 clarify as components of the Acne Repair Kit
 

Also be advised that we attribute the acne claims on the labeling of the "Acne Repair Kit" to "Hyaluronic Moisturizer HM-50 hydrate" and "Sulfur Mask SMT-2 clarify" when these products are included as components of the kit to be used in conjunction with each other and the other two components of the kit for the treatment of acne. Therefore, the "Hyaluronic Moisturizer HM-50 hydrate" and the "Sulfur Mask SMT-2 clarify" are mugs and subject to the requirements of the OTC Final Monograph for Topical Acne Dmg Products (21 C.F.R. Part 333, Subpart D). "Hyaluronic Moisturizer HM-50 hydrate" and the "Sulfur Mask SMT-2 clarify" are neither formulated nor labeled in conformance with this final monograph.
 

Therefore, the "Hyaluronic Moisturizer HM-50 hydrate" and "Sulfur Mask SMT-2 clarify" are "new drugs" under section 201(p) of the Act [21 U.S.C. § 321 (p)] when they are included as components of the "Acne Repair Kit" and as such the kit 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)].
 

In addition, when they are included as components of the "Acne Repair Kit" the "Hyaluronic Moisturizer HM-50 hydrate" and "Sulfur Mask SMT-2 clarify" are misbranded under sections 502(f)(1) and (f)(2) of the Act [21 U.S.C. §§ 352(f)(1) and (f)(2)] because their labeling does not bear the indications, directions, and warnings required by the final monograph. See 21 C.F.R. § 333.350.
 

For your information, the "Drug Facts" labeling requirements under 21 C.F.R. § 201.66(c)(8) indicates that the term "inactive ingredients" must be used for listing all ingredients that are not "active."
 

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.
 

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. 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. Also, please note that if you are no longer marketing (these) product(s), you must update the Drug Listing files in accordance with 21 C.F.R. § 207.30 (a)(2).
 

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 conection. We acknowledge the commitment in your October 7, 2009 response to temporarily cease manufacturing drug products. Please notify the Agency when you intend to resume manufacturing operations. We note that for several violations, you did not indicate when conective actions (e.g., revised SOPs, training, validation, etc.) would be implemented. Prior to resumption of manufacturing effective corrective actions should be fully implemented.
 

In addition, based upon the nature and number of violations, we recommend that you engage a third party consultant having appropriate CGMP expertise to assess your firm's facility, procedures, processes, and systems to ensure that future drug products have their appropriate identity, strength, quality, and purity.

Your written response should be sent to:
 

Daniel W. Cline
Acting Compliance Branch Director,
U.S. Food and Dmg Administration
19701 Fairchild
Irvine, CA 92612-2506
 

If you have question a regarding any issue in this letter, please contact Dr. Raymond W. Bmllo, Compliance Officer at (949) 608-2918.
 

Sincerely,
/S/

Alonza E. Cruse

District Director
Los Angeles District
 

cc: Branch Chief
Food and Drug Branch
California Department of Public Health
1500 Capitol Ave. - MS 7602
P.O. Box 997413
Sacramento, CA 95899-7413

____________________________________________________

1 e.g., list of active ingredients, excipients, materials, equipment, equipment mixing times and speed, personnel, weights, volumes, and process parameter ranges.
 

2 The TFM for Topical Acne Drug Products was issued on January 15, 1985. See 50 Fed. Reg. 2172. On August 16, 1991, FDA issued a final rule in the form of a final monograph establishing conditions under which OTC topical acne drug products are generally recognized as safe and effective and not misbranded (56 Fed. Reg. 41008). However, the final rule did not include final agency action on the OTC topical acne active ingredient benzoyl peroxide. However, on March 4, 2010, the FDA issued a final rule to include benzoyl peroxide at 2.5 to 10 percent as a generally recognized safe and effective active ingredient in OTC topical acne drug products (75 Fed. Reg. 9767). In addition, this final rule includes new warnings and directions required for OTC topical acne drug products that contain benzoyl peroxide as an active ingredient. This rule is not effective until March 4, 2011. You must ensure your OTC topical acne products that contain benzoyl peroxide as an active ingredient are consistent with tlris final rule by that date.
 

Until that date, to market under the OTC Drug Review your OTC topical acne drug products that contain benzoyl peroxide as an active ingredient must be: 1) consistent in formulation and labeling with the TFM for OTC topical acne products published in the Federal Register on Jannary 15, 1985 (50 Fed. Reg. 2172) or 2) marketed in the United States on or before the inception of the OTC Drug Review.