WARNING LETTER
Soluciones Cosmeticas, SA de CV
MARCS-CMS 609057 —
August 04, 2020
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
Mr. David Ali
Recipient Title
CEO
Soluciones Cosmeticas, SA de CV
Avenida Ano De Juarez 110,
Otro Granjas San Antonio
Iztapalapa
,
CDMX
Mexico
Issuing Office:
Center for Drug Evaluation and Research | CDER
United States
Warning Letter 320-20-42
August 4, 2020
Dear Mr. Ali:
Your firm recently registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of drug products manufactured at your facility: consumer antiseptic hand rubs (also referred to as consumer hand sanitizers) labeled as BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer and BERSIH HAND SANITIZER GEL Fragrance Free (referred to collectively as “Bersih HAND SANITIZER drug products”). These drug products were manufactured at your facility, Soluciones Cosmeticas SA de CV, FEI 3011274338, at Avenida Ano De Juarez 110, Otro Granjas San Antonio, Iztapalapa, Ciudad De Mexico MX and, following an attempted import into the United States, were detained and refused admission at the border.
The results of FDA laboratory testing demonstrated that batches of your Bersih HAND SANITIZER drug products are adulterated within the meaning of section 501(d)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(d)(2), in that a substance was substituted wholly or in part therefor. In addition, these products are adulterated within the meaning of section 501(a)(2)(B), 21 U.S.C. 351(a)(2)(B), in that the substitution demonstrates that the quality assurance within your facility is not functioning in accordance with Current Good Manufacturing Practice (CGMP) requirements.
In addition these drug products are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a), and are misbranded under sections 502(j), (a) and (e) of the FD&C Act, 21 U.S.C. 352(j), (a) and (e). Introduction or delivery for introduction of these products into interstate commerce is prohibited under sections 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a). These violations are described in more detail below.
Adulteration Violations
Your drug product, BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer, is labeled to contain 70% volume/volume (v/v) of the active ingredient alcohol (ethanol). However, FDA laboratory testing of batches of this product detained at the border found that your  Antiseptic Alcohol 70% Topical Solution Hand Sanitizer contained an average of 44% ethanol and 30% of methanol v/v. Additionally, BERSIH HAND SANITIZER GEL is labeled to contain 70% v/v of the active ingredient alcohol (ethanol). However, FDA laboratory testing of batches of this product detained at the border found that the product contained 67% ethanol and 1.6% methanol v/v. Therefore, these hand sanitizer drug products are adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient of ethanol was substituted wholly or in part with methanol, a dangerous chemical when in contact with human skin or ingested.
Methanol is not an acceptable ingredient for hand sanitizers and should not be used due to its toxic effects. Skin exposure to methanol can cause dermatitis, as well as transdermal absorption with systemic toxicity. Substantial methanol exposure can result in nausea, vomiting, headache, blurred vision, permanent blindness, seizures, coma, permanent damage to the nervous system, or death. Although all persons using these products on their hands are at risk, young children who accidentally ingest these products and adolescents and adults who drink these products as an alcohol (ethanol) substitute are most at risk for methanol poisoning.
On July 1, 2020, FDA held a teleconference with you and your registered U.S. agent, Logicargo US Customs & Bonded Carrier Solutions LLC. We recommended you consider removing all of your firm’s hand sanitizer drug products currently in distribution to the U.S. market. As you had not taken action upon our request, on July 2, 2020 FDA notified the public of methanol contamination of your hand sanitizer at the following website:
https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
.
On July 10, 2020, FDA held a subsequent teleconference with you and your outside counsel to discuss the serious health implications regarding methanol contamination. Subsequently you agreed to recall all of your hand sanitizer drug products, and verified that all your your BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer was refused admission to the Unitied States On July 14, 2020, you issued a voluntary nationwide recall of BERSIH HAND SANITIZER GEL due to potential presence of undeclared methanol (Wood Alcohol), as noted on the following FDA website:
https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/soluciones-cosmeticas-issues-voluntary-nationwide-recall-bersih-hand-sanitizer-gel-due-potential
In response to this letter provide the following:
• A detailed investigation into how hand sanitizer drug products manufactured at your facility, and labeled as containing ethanol, were substituted in part or in whole with methanol.
• A list of all raw materials used to manufacture all of your hand sanitizer drug products, including the suppliers’ names, addresses, and contact information.
• A list of all batches of any hand sanitizer drug products shipped to the United States by your firm, and a full reconciliation of all material you distributed.
• Copies of the complete batch records for all batches distributed to the U.S.
• During discussion with FDA, you indicated that one shipment FDA tested and found to have methanol contamination was in fact intended for research purposes only. However, the labeling was indicative of drugs for consumer use (e.g., the labeling included a Drug Facts label) and the shipment was declared as for human use. Accordingly, when you provide a full list of batches distributed, include any you contend were manufactured for research purposes only.
The substitution and methanol contamination in hand sanitizer drug products manufactured in your facility is evidence that the quality assurance within your facility is not functioning in accordance with CGMP requirements under section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
1
Unapproved New Drug and Misbranding Violations
BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer and BERSIH HAND SANITIZER GEL are “drugs” as defined by section 201(g)(1)(B) of the FD&C 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 FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body. Specifically, these products are intended as topical antiseptics.
Examples of claims observed on the BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer product label, that provide evidence of the intended use (as defined in 21 CFR 201.128) of the product include, but may not be limited to, the following:
“Hand Sanitizer . . . Drug Facts . . . Uses[s] Hand Sanitizer to help reduce bacteria that potentially can cause disease.”
Examples of claims observed on the BERSIH HAND SANITIZER GEL product label, that provide evidence of the intended use (as defined in 21 CFR 201.128) of the product include, but may not be limited to, the following:
“HAND SANITIZER . . . SUPPORTS KILLING 99.9% OF GERMS . . . Drug Facts . . . Use to help reduce bacteria on the skin.”
These hand sanitizer products are “new drugs” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because they are not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in their labeling. New drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for either of these hand sanitizer products, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer and BERSIH HAND SANITIZER GEL drug products are GRASE for use under the conditions suggested, recommended, or prescribed in their labeling. Accordingly, these products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).
We note that over-the-counter (OTC) topical antiseptic products have been the subject of rulemaking under the Agency’s OTC Drug Review. In particular, such products were addressed in a tentative final monograph (TFM) entitled “Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Health-Care Antiseptic Drug Products,” Proposed Rule, 59 FR 31402 (June 17, 1994) (1994 TFM), as further amended by the “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016) and the “Safety and Effectiveness of Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; and Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 80 FR 25166 (May 1, 2015). Over the course of these rulemakings, benzalkonium chloride, ethyl alcohol, and isopropyl alcohol were classified as Category III, meaning that additional safety and effectiveness data are needed to support a determination that a drug product containing one of these active ingredients would be GRASE for use as a consumer or health care personnel antiseptic rub.
The Coronavirus Aid, Relief, and Economic Security Act (CARES Act), enacted on March 27, 2020, added section 505G to the FD&C Act, which addresses nonprescription drugs marketed without an approved application. Under 505G(a)(3) of the FD&C Act, drugs that were classified as Category III in a TFM that is the most recently applicable proposal or determination for such drug issued under 21 CFR Part 330 – and that were not classified in such a TFM as Category II for safety or effectiveness -- are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM, including the active ingredient, and comply with all other applicable requirements for nonprescription drugs.
However, your Bersih HAND SANITIZER drug products do not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rub proposed rule and the 2015 Health Care Antiseptic proposed rule, nor any other TFM or final rule, and do not meet the conditions under section 505G(a)(3) of the FD&C Act, as added by the CARES Act, for marketing without an approved application under section 505.
2
According to the product label, BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer purportedly contains the active ingredient ethyl alcohol (ethanol) 70% v/v. However, as previously discussed, FDA laboratory analyses revealed that a sample of BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer contains a concentration of ethanol that is far less than the 70% declared on the label and far less than the amount of ethanol described in the 1994 TFM.
3
Such a product does not conform with the TFM, nor is it consistent with the formulations described in FDA’s temporary policies for hand sanitizers during the COVID-19 public health emergency.
FDA laboratory analyses also revealed that samples of your Bersih HAND SANITIZER drug products contain significant concentrations of the undeclared ingredient methyl alcohol (methanol). Use of methanol as an active ingredient is not in conformance with the TFM, nor is it included in the formulations described in FDA’s Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) Guidance for Industry. Furthermore, methanol is not acceptable as an inactive ingredient in hand sanitizers. As previously discussed, methanol has significant and sometimes fatal toxic effects and, therefore, does not meet the requirements under 21 CFR 330.1(e) that an OTC monograph drug contain only safe and suitable inactive ingredients.
4
Additionally, these methanol-containing drug products, BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer and BERSIH HAND SANITIZER GEL, are misbranded under sections 502(j), (a), and (e) of the FD&C Act, 21 U.S.C. 352(j), (a), and (e). They are misbranded under section 502(j) of the FD&C Act, 21 U.S.C. 352(j), because they are dangerous to health when used according to their labeling as hand sanitizers. As previously stated, skin exposure to methanol could lead to systemic absorption. Substantial methanol exposure can potentially result in, among other things, blindness, permanent nervous system damage, and even death. These hand sanitizers are misbranded under section 502(a) of the FD&C Act, 21 U.S.C 352(a), because their labeling is false and misleading. As noted above, BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer is labeled to contain ethyl alcohol 70% v/v. However, FDA laboratory analysis revealed that a sample of this product contains less ethyl alcohol than indicated on the labeling and instead contains significant concentrations of methyl alcohol (methanol), an ingredient that is not declared on the product labels.
Section 201(n) of the FD&C Act, 21 U.S.C. 321(n), provides that “in determining whether the labeling or advertising is misleading there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in the light of such representations or material with respect to consequences which may result. . ..” As such, the label representation that BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer contains 70% ethyl alcohol when it does not, as well as the failure of both the product labels to disclose the presence of the methyl alcohol in the products, causes these products to be misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). Lastly, the failure of these products to list methyl alcohol (methanol) as an ingredient on their labels causes them to be misbranded under section 502(e)(1)(A) of the FD&C Act, 21 U.S.C. 352(e)(1)(A).
The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).
Conclusion
The violations cited in this letter are not intended to be an all-inclusive list of violations associated with your drug products. You are responsible for investigating and determining the causes of these violations and for preventing their recurrence or the occurrence of other violations.
Note that FDA placed all drugs and drug products manufactured by your firm on Import Alert 66-78 on July 10, 2020.
All drugs and drug products manufactured by your firm will remain listed on this import alert until the concerns with your drugs are adequately addressed and verified by FDA.
If you decide you want to manufacture drugs for the United States in the future, request a Regulatory Meeting to discuss corrective actions required prior to an FDA inspection. Until FDA is able to inspect your facility, we may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.
In addition, shipments of articles manufactured at Soluciones Cosmeticas SA de CV, Avenida Ano De Juarez 110, Otro Granjas San Antonio, Iztapalapa, Ciudad De Mexico MX into the United States are subject to refusal of admission pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3) in that they appear adulterated under section 501 of the FD&C Act, 21 U.S.C. 351.
After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to correct your violations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration.
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov
Identify your response with FEI 3011274338 and ATTN: Daniel W. Brisker.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Registered US Agent
Alejandro R Zamudo
Logicargo US Customs & Bonded Carrier Solutions LLC
410 Nafta Blvd Laredo TX 78045
CC:
Outside Counsel
Jessica P. O'Connell
Covington & Burling LLP
One CityCenter, 850 Tenth Street, NW
Washington, DC 20001-4956
_______________________
1
Due to an increased demand for alcohol-based hand sanitizers during the COVID-19 pandemic, FDA published the Guidance for Industry:
Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19)
on March 19, 2020, and subsequently updated the guidance on March 27, April 15 and June 1 of 2020. This guidance communicates the Agency’s temporary policy that we do not intend to take action against firms for CGMP violations under section 501(a)(2)(B) of the FD&C Act if such firms prepare alcohol-based hand sanitizers for consumer use (or for use as health care personnel hand rubs) during the public health emergency, provided certain circumstances described in the guidance are present. These circumstances include preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. In addition to the violative sample results detailed above that demonstrate the presence of methanol in your hand sanitizer products, review of the formulations on your drug product labeling further indicate that such products are not prepared consistent with FDA’s temporary policy set forth in the guidance. Therefore, these products do not fall within the Agency’s temporary policy not to take action against firms manufacturing hand sanitizer products for violations of section 501(a)(2)(B) of the FD&C Act.
2
Furthermore, BERSIH Antiseptic Alcohol 70% Topical Solution Hand Sanitizer and BERSIH HAND SANITIZER GEL do not fall under any temporary policy for hand sanitizers that FDA has implemented in response to the COVID-19 public health emergency. See
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-guidance-production-alcohol-based-hand-sanitizer-help-boost
3
The 1994 TFM, which does not distinguish between antiseptic hand washes and rubs, proposed for antiseptic handwashes and healthcare personnel handwashes an alcohol concentration of 60 to 95% by volume in an aqueous solution. 59 FR at 31442. Later amendments to the 1994 TFM distinguished between antiseptic hand washes and rubs, and between consumer and healthcare personnel antiseptics, but did not change the alcohol concentration originally proposed in 1994.
4
An inactive ingredient used in over-the-counter (OTC) monograph drugs must meet the requirements of 21 CFR 330.1(e), which requires, among other things, that inactive ingredients must be safe in the amount administered.
Content current as of:
08/11/2020
Regulated Product(s)
Drugs