| Public Health Service Food and Drug Administration |
San Francisco District |
Department of Health and Human ServicesWARNING LETTER
Via UPS
Delivery Signature Requested
April 18, 2011
Richard D. Malmborg, President and CEO
Oh So Clean, Inc dba CleanWell Company
315 Pacific Avenue
San Francisco, CA 94111
REF: FEI 3006616549
Dear Mr. Malmborg:
From August 16 through 30, 2010, investigator(s) from the Food and Drug Administration (FDA) conducted an inspection at your pharmaceutical manufacturing facility, Oh So Clean, Inc dba CleanWell Company (CleanWell), in San Francisco, California. CleanWell, located at 315 Pacific Avenue, San Francisco, California, is an own-label distributor that has entered into agreements with contract manufacturers to manufacture all of its own-label products. You also oversee batch release for the products distributed under your name, including conducting certain testing.
During the inspection, our investigator collected labeling for CleanWell All-Natural Foaming Hand Sanitizer, CleanWell All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes, and CleanWell All-Natural Antibacterial Foaming Handsoap drug products. As explained below, these products are unapproved new drugs in violation of section 505(a) of the Act [21 U.S.C. § 355(a)] and misbranded under section 502(e) of the Act [21 U.S.C § 352(e)].
Additionally, we identified significant violations of Current Good Manufacturing Practice (CGMP) regulations for Finished Pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211. These violations cause your 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, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.
We have reviewed your firm’s response dated September 15, 2010, and note that it lacks sufficient corrective actions.
Specific violations observed during the inspection include, but are not limited, to the following:
Unapproved and Misbranded OTC Drugs
Below is an analysis of the regulatory status of CleanWell All-Natural Foaming Hand Sanitizer, CleanWell All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes and CleanWell All-Natural Antibacterial Foaming Handsoap drug products, which includes excerpts of the violative labeling and the specific new drug charges. Note that this is not intended to be an all-inclusive description of all violative labeling for your OTC drug products.
CleanWell All-Natural Foaming Hand Sanitizer
The product labeling for CleanWell All-Natural Foaming Hand Sanitizer represents the product as an OTC topical antimicrobial hand sanitizer. The Drug Facts Panel on the label of CleanWell All-Natural Foaming Hand Sanitizer indicates that the product has a single active ingredient, thymus vulgaris oil (Thymol 0.05%) for the purpose of “sanitizer.”
However, elsewhere on this product’s immediate label, quoted below, a formulation of “essential plant oils,” is described as providing an antimicrobial effect:
“All-Natural CleanWell ™ is a patented formulation of essential plant oils proven to kill 99.99% of germs including MRSA, Salmonella, Staph, and E.coli.”
In addition, the immediate label of this product includes reference to your website, www.cleanwelltoday.com. Labeling on this website represents and suggests “essential plant oils” are active ingredients that have an antimicrobial effect:
“CleanWell hand sanitizers are made with a patented formulation of essential plant oils lab proven to kill 99.9% of the harmful germs that can make you sick.”
Further, a “Technology Brief” entitled “Cleanwell Botanical Germ-Killing Technology,” which you offer for download on your website (http://www.cleanwelltoday.com/downloads/CleanWell_Techbrief.pdf), states:
“CleanWell’s active ingredient is a proprietary, fast-acting, broad-spectrum antimicrobial created from a patented blend of natural thyme and other essential plant oils. . . . The heightened activity and novel combination of oils has proven highly effective at eliminating harmful transient bacteria, while leaving beneficial resident bacteria and soft, healthy skin.”
The product’s uses are described in the product name itself, CleanWell All-Natural Foaming Hand Sanitizer, and the following statements on its label:
“All-Natural CleanWell™ is a patented formulation of essential plant oils proven to kill 99.99% of germs including MRSA, Salmonella, Staph and E. coli.”
“Use: Sanitize hands when you can’t wash with soap and water”
“Kills 99.99% of germs naturally”
Labeling on your website (www.cleanwelltoday.com) also includes the following statements about CleanWell All-Natural Foaming Hand Sanitizer and its uses:
“Kills 99.9% of harmful germs on contact. Including MRSA (resistant Staph), E. Coli and Salmonella.”
Your website also includes a “Technology Brief” entitled “Cleanwell Botanical Germ-Killing Technology” (http://www.cleanwelltoday.com/downloads/CleanWell_Techbrief.pdf) that has the following information about CleanWell All-Natural Foaming Hand Sanitizer:
CleanWell Hand Sanitizer Laboratory Data
Testing Method Organisms CleanWell Results GLP Bacteria Kill (In Vitro) • MRSA
• Staphylococcus aureus
• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Escherichia coli>99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
Based on the labeling described above, CleanWell All-Natural Foaming Hand Sanitizer is a “drug” as defined by section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because it is intended for use in the cure, treatment, mitigation, or prevention of disease, or is intended to affect the structure or any function of the body of man.
However, we are not aware of sufficient evidence that shows CleanWell All-Natural Foaming Hand Sanitizer is generally recognized as safe and effective for the uses noted above. In particular, we are not aware of evidence that this product is safe and effective in preventing individuals from becoming infected by E. coli, Klebsiella pneumoniae, MRSA, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus.
In addition, such consumer-directed claims are not described in any OTC final monograph, tentative monograph or any of the rulemakings being considered under the OTC Drug Review. Also, we are unaware of any evidence that a product so formulated and labeled was marketed in the United States on or before the inception of the OTC Drug Review. As such, CleanWell All-Natural Foaming Hand Sanitizer does not qualify for evaluation under the OTC Drug Review without submission of a time and extent application under 21 CFR 330.14 and a subsequent determination of eligibility.
Therefore, CleanWell All-Natural Foaming Hand Sanitizer 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)].
Further, the product is misbranded under section 502(e) of the Act [21 U.S.C § 352(e)] because its label does not bear the established name and quantity or proportion of each of its active ingredients. As described above, only “Thymus Vulgaris Oil (Thymol 0.05%)” is identified as an active ingredient, by established name, on the product label, but other labeling for the product indicates that a blend of essential plant oils are active ingredients because they provide an antibacterial effect.
CleanWell All-Natural Hand Sanitizer
The product labeling for CleanWell All-Natural Hand Sanitizer represents the product as an OTC topical antimicrobial hand sanitizer. The Drug Facts Panel on the label of CleanWell All-Natural Hand Sanitizer indicates that the product has a single active ingredient, thymus vulgaris oil (Thymol 0.05%) for the purpose of “sanitizer.”
However, elsewhere on this product’s immediate label, quoted below, a formulation of “essential plant oils,” is described as providing an antimicrobial effect:
“All-Natural CleanWell ™ is a patented formulation of essential plant oils proven to kill 99.99% of germs”
In addition, the immediate label of this product includes reference to your website, www.cleanwelltoday.com. Labeling on this website represents and suggests “essential plant oils” are active ingredients that have an antimicrobial effect:
“CleanWell hand sanitizers are made with a patented formulation of essential plant oils lab proven to kill 99.9% of the harmful germs that can make you sick.”
Further, a “Technology Brief” entitled “Cleanwell Botanical Germ-Killing Technology,” which you offer for download on your website http://www.cleanwelltoday.com/downloads/CleanWell_Techbrief.pdf), states:
“CleanWell’s active ingredient is a proprietary, fast-acting, broad-spectrum antimicrobial created from a patented blend of natural thyme and other essential plant oils. . . . The heightened activity and novel combination of oils has proven highly effective at eliminating harmful transient bacteria, while leaving beneficial resident bacteria and soft, healthy skin.”
The product’s uses are described in the product name itself, CleanWell All-Natural Hand Sanitizer, and the following statements on its label:
“All-Natural CleanWell™ is a patented formulation of essential plant oils proven to kill 99.99% of germs”
“Use: Sanitize hands when you can’t wash with soap and water”
“Kills 99.99% of germs naturally”
Labeling on your website (www.cleanwelltoday.com) also includes the following statements about CleanWell All-Natural Hand Sanitizer and its uses:
“Kills 99.9% of harmful germs on contact. Including MRSA (resistant Staph), E. Coli and Salmonella.”
Your website also includes a “Technology Brief” entitled “Cleanwell Botanical Germ-Killing Technology” (http://www.cleanwelltoday.com/downloads/CleanWell_Techbrief.pdf) that has the following information about CleanWell All-Natural Hand Sanitizer:
CleanWell Hand Sanitizer Laboratory Data
• MRSATesting Method Organisms CleanWell Results GLP Bacteria Kill (In Vitro)
• Staphylococcus aureus
• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Escherichia coli >99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
>99.99% (15 sec)
Based on the labeling described above, CleanWell All-Natural Hand Sanitizer is a “drug” as defined by section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because it is intended for use in the cure, treatment, mitigation, or prevention of disease, or is intended to affect the structure or any function of the body of man.
However, we are not aware of sufficient evidence that shows CleanWell All-Natural Hand Sanitizer is generally recognized as safe and effective for the uses noted above. In particular, we are not aware of evidence that this product is safe and effective in preventing individuals from becoming infected by E. coli, Klebsiella pneumoniae, MRSA, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus.
In addition, such consumer-directed claims are not described in any OTC final monograph, tentative monograph or any of the rulemakings being considered under the OTC Drug Review. Also, we are unaware of any evidence that a product so formulated and labeled was marketed in the United States on or before the inception of the OTC Drug Review. As such, CleanWell All-Natural Hand Sanitizer does not qualify for evaluation under the OTC Drug Review without submission of a time and extent application under 21 CFR 330.14 and a subsequent determination of eligibility.
Therefore, CleanWell All-Natural Hand Sanitizer 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)].
Further, the product is misbranded under section 502(e) of the Act [21 U.S.C § 352(e)] because its label does not bear the established name and quantity or proportion of each of its active ingredients. As described above, only “Thymus Vulgaris Oil (Thymol 0.05%)” is identified as an active ingredient, by established name, on the product label, but other labeling for the product indicates that a blend of essential plant oils are active ingredients because they provide an antibacterial effect.
CleanWell All-Natural Hand Sanitizing Wipes
The product labeling for CleanWell All-Natural Hand Sanitizing Wipes represents the product as an OTC topical antimicrobial skin cleanser. (While the product name refers to hands only, elsewhere on the label, it is indicated for use on the face as well.) The Drug Facts Panel on the label of CleanWell All- Natural Hand Sanitizing Wipes indicates that the product has a single active ingredient, thymus vulgaris oil, (Thymol 0.05%), for the purpose of “sanitizer.”
However, elsewhere on this product’s immediate label, quoted below, a formulation of “essential plant oils,” is described as providing an antimicrobial effect:
“All-Natural CleanWell™ a patented formulation of essential plant oils proven to kill 99.99% of germs ”
In addition, the immediate label of this product directs users to visit www.cleanwelltoday.com. Labeling on this website represents and suggests “essential plant oils” are active ingredients that have an antimicrobial effect:
“CleanWell hand sanitizers are made with a patented formulation of essential plant oils lab proven to kill 99.9% of the harmful germs that can make you sick.”
The product’s uses are described in the product name itself, CleanWell All-Natural Hand Sanitizing Wipes, and statements on its label including:
“Kills 99.99% of germs naturally”
“For hands and face”
“Use: Sanitize hands when you can’t wash with soap and water”
Labeling on your website (www.cleanwelltoday.com) also includes the following statements about CleanWell All-Natural Hand Sanitizing Wipes and its uses:
“Kills 99.9% of harmful germs on contact. Including MRSA (resistant Staph), E. Coli and Salmonella.”
Based on the labeling described above, CleanWell All-Natural Hand Sanitizing Wipes is a “drug” as defined by section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because it is intended for use in the cure, treatment, mitigation, or prevention of disease, or is intended to affect the structure or any function of the body of man.
However, we are not aware of sufficient evidence that shows CleanWell All-Natural Hand Sanitizing Wipes is generally recognized as safe and effective for the uses noted above. In particular, we are not aware of sufficient evidence that this product is safe and effective in preventing individuals from becoming infected by E. coli, MRSA and Salmonella.
In addition, such consumer-directed claims are not described in any OTC final monograph, tentative monograph or any of the rulemakings being considered under the OTC Drug Review. Also, we are unaware of any evidence that a product so formulated and labeled was marketed in the United States on or before the inception of the OTC Drug Review. As such, CleanWell All- Natural Hand Sanitizing Wipes does not qualify for evaluation under the OTC Drug Review without submission of a time and extent application under 21 CFR 330.14 and a subsequent determination of eligibility.
Therefore, CleanWell All-Natural Hand Sanitizing Wipes 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)].
Further, the product is misbranded under section 502(e) of the Act [21 U.S.C § 352(e)] because its label does not bear the established name and quantity or proportion of each of its active ingredients. As described above, only “Thymus Vulgaris Oil, (Thymol 0.05%)” is identified as an active ingredient, by established name, on the product label, but other labeling for the product indicates that a blend of essential plant oils are active ingredients because they provide an antibacterial effect.
CleanWell All-Natural Antibacterial Foaming Handsoap
The product labeling for CleanWell All Natural Antibacterial Foaming Handsoap represents the product as an OTC antimicrobial hand soap. The Drug Facts Panel on the label of CleanWell All-Natural Antibacterial Foaming Handsoap indicates that the product has a single active ingredient, thymus vulgaris oil, (Thymol 0.04%), described as providing an antibacterial effect.
However, elsewhere on this product’s immediate label, quoted below, a formulation of “essential plant oils,” is described as providing an antimicrobial effect:
“All-Natural CleanWell™ is a proprietary formulation of essential plant oils proven to kill 99.99% of germs including MRSA, Salmonella, Staph and E. coli.”
In addition, the immediate label of this product directs users to visit www.cleanwelltoday.com. Labeling on this website similarly identifies “essential oils as active ingredients:
“Each hand soap is infused with White Tea & Aloe and made with a patented formulation of essential plant oils proven to kill 99.99% of harmful germs.”
The product’s uses are described in the product name itself, CleanWell All-Natural Antibacterial Foaming Handsoap, and the following statements on its label:
“Use: For handwashing to help eliminate bacteria on skin”
“Proven to kill 99.99% of germs”
“All-Natural CleanWell ™ is a proprietary formulation of essential plant oils proven to kill 99.9% of germs including MRSA, Salmonella, Staph and E. coli”
Labeling on your website (www.cleanwelltoday.com) includes statements such as the following about CleanWell All Natural Antibacterial Foaming Handsoap and its uses:
“Kills 99.9% of harmful germs on contact. Including MRSA (resistant Staph), E. Coli and Salmonella.”
Based on the labeling described above, CleanWell All-Natural Antibacterial Foaming Handsoap is a “drug” as defined by section 201(g)(1) of the Act [21 U.S.C. § 321(g)(1)] because it is intended for use in the cure, treatment, mitigation, or prevention of disease, or is intended to affect the structure or any function of the body of man.
However, we are not aware of sufficient evidence that shows CleanWell All-Natural Antibacterial Foaming Handsoap is generally recognized as safe and effective for the uses noted above. In particular, we are not aware of evidence that this product is safe and effective in preventing individuals from becoming infected by E. coli, Methicillin Resistant Staphylococcus aureus (MRSA), and Salmonella infections.
In addition, such consumer-directed claims are not described in any OTC final monograph, tentative monograph or any of the rulemakings being considered under the OTC Drug Review. Also, we are unaware of sufficient evidence that a product so formulated and labeled was marketed in the United States on or before the inception of the OTC Drug Review. As such, CleanWell All Natural Antibacterial Foaming Handsoap does not qualify for evaluation under the OTC Drug Review without submission of a time and extent application under 21 CFR 330.14 and a subsequent determination of eligibility.
Therefore, CleanWell All Natural Antibacterial Foaming Handsoap 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)].
Further, the product is misbranded under section 502(e) of the Act [21 U.S.C § 352(e)] because its label does not bear the established name and quantity or proportion of each of its active ingredients. As described above, only “Thymus Vulgaris oil, (Thymol 0.04%)” is identified as an active ingredient, by established name, on the product label, but other labeling for the product indicates that a blend of essential plant oils also are active ingredients because they provide an antibacterial effect.
Based on the product labeling claims, CleanWell All-Natural Foaming Hand Sanitizer, CleanWell All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes and CleanWell All-Natural Antibacterial Foaming Handsoap are OTC topical antimicrobials. For your information and guidance, OTC topical antimicrobials include OTC healthcare antiseptics and OTC first aid antiseptics, which are being evaluated under FDA's OTC Drug Review. Tentative Final Monographs (TFMs) for these products were published in the Federal Register of 59 Fed. Reg. 31402 (June 17, 1994) and 56 FR 336444 (July 22, 1991). These TFMs are available on FDA's Internet website at:
Pending a final monograph, the agency does not object to the marketing of OTC drugs that meet the formulation and labeling requirements described in the TFM.1 However, your products’ formulation and labeling are not consistent with any of these TFMs.
To be included in the OTC Drug Review, a product’s formulation and labeling must have existed in the marketplace in the United States on or before the inception of the OTC Drug Review, or the product must have been determined to be eligible for inclusion in accordance with the “time and extent” application (TEA) procedures of 21 CFR 330.14. As formulated and labeled, CleanWell All-Natural Foaming Hand Sanitizer, CleanWell, All-Natural Hand Sanitizer, CleanWell All-Natural Hand Sanitizing Wipes and CleanWell All-Natural Antibacterial Foaming Handsoap do not qualify for evaluation under the review. First, we are not aware of OTC antimicrobial products like the CleanWell products named above that existed on or before the inception of the OTC drug Review that contained thymus vulgaris oil and other “essential oils” as active ingredients. 2 Second, the product claims listed above, such as indications for use that include the prevention of infection from MRSA, are not described in any of the rulemakings. FDA has not determined these products eligible for inclusion in the OTC Drug Review via the “time and extent” application (TEA) procedures of 21 CFR 330.14. Therefore, such claims and antimicrobial products with such claims are not being considered under the OTC Drug Review.
CGMP Violations
As indicated previously, your firm distributes under its own name drug products that are manufactured for you by contract manufacturers. In general, FDA considers it to be the responsibility of the contract manufacturer to assess a batch’s conformance with specifications, production controls, and procedures before it leaves their control in accordance with CGMP regulations at 21 C.F.R. Part 211. However, since your firm has undertaken some responsibility for releasing drug batches, in lieu of the contract manufacturer, your firm’s operations must satisfy the requirements of 21 C.F.R.§ 211.22, but fail to do so. Specifically:
1. Your firm has failed to establish and follow written responsibilities and procedures applicable to the quality control unit [21 C.F.R. § 211.22(d)].
Your firm does not have documentation addressing the basic roles, responsibilities, and procedures for your QCU. For example, your firm does not have a written procedure for the investigation of Out-of-Specification (OOS) results, to ensure that investigations are adequately conducted and documented. In the absence of such a procedure, you failed to ensure that an adequate investigation was conducted of the active ingredient potency OOS failure for lot (b)(4), Hand Sanitizer Wipes, which your firm performed. An adequate OOS procedure is an additional control to ensure that consistent interpretation of data and findings are used to conduct a proper evaluation of OOS test results.
Your response is inadequate because you do not define the process for your QCU to review and ensure that a proper investigation is conducted.
2. Your quality control unit does not have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality, and purity of the drug product [21 C.F.R. § 211.22(c)].
There is no indication that the QCU has exercised oversight for procedures or specifications impacting the identity, strength, quality, and purity of the drug product. For example, your practices for batch release, which do not appear to be approved by a QCU, are not adequate because the same employee at your firm conducts the quality control testing and approves the batch release. This practice has allowed incorrect data to be reported on the Certificate of Analysis (COA), which was used to release the drug products. Your failure to have an additional independent review of the test results has potentially allowed drug products to be released without meeting drug product specifications.
Your response is inadequate because it fails to describe the changes that would be implemented in your procedures to ensure an effective and appropriate review of the laboratory records before batch release. In addition, your response states that your firm will conduct a six month testing period to evaluate the revised QCU process. However, your firm has not provided details concerning the implementation process and/or an analysis of the effectiveness of your procedure.
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. Anyone who distributes an adulterated or misbranded drug has committed a prohibited act under the Act.
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.
As stated above, you must cease manufacturing and distributing all your unapproved new drug products. 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. 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 send your reply to the attention:
Darlene Almogela
Director, Compliance Branch
U.S. Food and Drug Administration
San Francisco District
1431 Harbor Bay Parkway
Alameda, CA 94502
If you have any questions regarding any issue in this letter, please contact Carl Lee, Compliance Officer at 510-337-6737.
Sincerely,
/S/
Barbara Cassens
District Director
1 Such marketing is subject to the risk that it may be necessary to reformulate and/or relabel such products or seek FDA approval through the NDA procedures of the Act [section 505] once a final monograph is in effect. Furthermore, OTC drugs found eligible for inclusion in the OTC Drug Review in accordance with the TEA procedures of 21 CFR 330.14 may be marketed under a TFM only when the requirements of 21 CFR 330.14(h) have been satisfied.
2 It is our position that thymus vulgaris oil and other essential oils in the CleanwelJ products are active ingredients because the labeling for these products indicates that these ingredients furnish pharmacological activity. 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 humans, would be considered an active ingredient.
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