WARNING LETTER
DMM Vission, S.A. de C.V.
MARCS-CMS 609797 —
June 03, 2021
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
Ma. de la Luz Escorza
Recipient Title
CEO
DMM Vission, S.A. de C.V.
Calle Lago Guija 234
Col. Agua Azul
57500
Ciudad Nezahualcoyotl
,
Méx.
Mexico
Issuing Office:
Center for Drug Evaluation and Research
United States
Warning Letter 320-21-48
June 03, 2021
Dear Ms. Escorza:
Your firm was registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of consumer antiseptic hand rub drug products (also referred to as consumer hand sanitizers) labeled as SYP HEALTH HAND SANITIZER ALCOHOL GEL and Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel. SYP HEALTH HAND SANITIZER ALCOHOL GEL was labeled as manufactured at your facility, and Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel was declared to be manufactured at your facility, DMM Vission, S.A. de C.V., FEI 3016833130, at Calle Lago Guija 234, Col. Agua Azul, Cuidad Nezahualcoyotl, Mexico. Following an attempt to import DMM Hand Sanitizer drug products into the United States, these products were detained and refused admission at the border.
The results of FDA laboratory testing of batches of these drug products detained at the border demonstrate that these drug products, labeled or declared to be manufactured at your facility, 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) of the FD&C Act (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, your Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL drug products are unapproved new drugs 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), (e), (f)(2), (x) and (ee) of the FD&C Act, 21 U.S.C. 352 (j), (a), (e), (f)(2), (x) and (ee). Lastly, SYP HEALTH HAND SANITIZER is also misbranded under 502 (i) of the FD&C Act, 21 U.S.C 352(i).
Introduction or delivery for introduction of such 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).
Adulteration Violations
SYP HEALTH HAND SANITIZER ALCOHOL GEL, labeled as manufactured at your facility, is labeled to contain 70% of the active ingredient ethyl alcohol (ethanol). However, FDA laboratory testing of a batch of SYP HEALTH HAND SANITIZER ALCOHOL GEL product detained at the border found that the product contained an average of 31% ethanol and an average of 2.3% methanol volume/volume (v/v).
Additionally, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel, declared to be manufactured at your facility, is labeled to contain 70% v/v of the active ingredient ethyl alcohol (ethanol). However, FDA laboratory testing of a batch of Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel product detained at the border found that the product contained an average of 22% ethanol and an average of 10% 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 August 21, 2020, FDA held a teleconference with you and Registrar Corp, your registered U.S. agent. We recommended you consider removing all of your firm’s hand sanitizer drug products currently in distribution from the U.S. market. On August 21, 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 September 8, 2020, you announced a voluntary nationwide recall for five lots of Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel 500ml and 1200ml bottles due to potential presence of undeclared methanol (Wood Alcohol), as noted on the following FDA webpage:
https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/dmm-vission-sa-de-cv-issues-voluntary-nationwide-recall-cleaner-hand-sanitizer-500-ml-and-1200-ml?utm_medium=email&utm_source=govdelivery
.
Additionally, the FDA contacted your firm’s consignees to recall. On September 24, 2020, one of your firm’s consignees, AA Products Inc., recalled one lot of SYP HEALTH HAND SANITIZER ALCOHOL GEL 500ml bottles.
In response to this letter, provide the following:
• A detailed investigation into how the drug products described above, which were declared or labeled as manufactured at your facility, and which were 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.
The substitution and methanol contamination in a drug product declared or labeled as manufactured in your facility demonstrates 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
Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL 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, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL are intended for use as consumer topical antiseptics.
Examples of claims observed on the Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL labeling that provide evidence of the intended use (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:
Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel:
“
Drug Facts
. . .
Purpose
. . . Antimicrobial
Use
: To help reduce bacteria on the skin. . . Directions: Wet hands thoroughly with product, gently rub into skin and allow to dry without wiping.
SYP HEALTH HAND SANITIZER ALCOHOL GEL:
DRUG FACTS:
. . . USES: hand sanitizer to help decrease bacteria on the skin. . . DIRECTIONS: pump as needed into your palms thoroughly spread on both hands, rub into skin until dry.
These topical antiseptic 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), unless they are lawfully marketed under section 505G of the Act (which is not the case for these products, as further described below) or under other exceptions not applicable here. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for these drug products, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL 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 had been the subject of rulemaking under FDA’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 “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) (Consumer Antiseptic Rubs Proposed Rule). Over the course of these rulemakings three active ingredients (benzalkonium chloride, ethyl alcohol (ethanol), and isopropyl alcohol) were classified in Category III for use in consumer antiseptic rub products, 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 rub.
Section 505G of the FD&C Act addresses nonprescription drugs marketed without an approved application. Under section 505G(a)(3) of the FD&C Act, drugs that were classified as Category III for safety or effectiveness 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 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.
However, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL do not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rue, nor any other TFM, proposed rule, or final rule, and do not meet the conditions under section 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505.
According to the product labels, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL purportedly contain the active ingredient ethyl alcohol (ethanol) 70%. However, as previously discussed, FDA laboratory analyses of batches of these products detained at the border demonstrated that Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL contain ethyl alcohol (ethanol) in a concentration that is less than the 70% stated on its product labels and less than the amount of ethyl alcohol (ethanol) described in the 1994 TFM.
2
Such products do not conform with the TFM or applicable requirements nor are they consistent with the formulations described in the guidances setting forth FDA’s temporary policies for hand sanitizers during the COVID-19 public health emergency.
3
FDA laboratory analyses also demonstrated that batches of Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL contain significant concentrations of the undeclared ingredient methyl alcohol (methanol). Use of methanol as an active ingredient is not in conformance with the 1994 TFM, nor is methanol 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 its inactive ingredients be safe and suitable.
4
Additionally, these methanol-containing drug products, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL, are misbranded under sections 502(j), (a), (e), (f)(2), (x) and (ee) of the FD&C Act, 21 U.S.C. 352(j), (a), (e), (x) and (ee). SYP HEALTH HAND SANITIZER ALCOHOL GEL is also misbranded under section 502(i) of the FD&C Act, 21 U.S.C 352(i).
These products 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, and 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 or misleading. As noted above, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL are labeled to contain ethyl alcohol (ethanol) 70%. However, FDA laboratory analyses of batches of these products demonstrate that the products contain a concentration of ethyl alcohol (ethanol) that is less than what is stated on the product labels and contain a significant concentration 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. . ..” Thus, the misleading representation of the concentration of the active ingredient ethyl alcohol (ethanol), and the failure of the product labels to disclose the presence of methyl alcohol (methanol) in the products, causes these products to be misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).
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).
Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER GEL are also misbranded under section 502(f)(2) of the FD&C Act, 21 U.S.C. 352(f)(2) because the product labels do not include all of the applicable warnings as required under 21 CFR 330.1(g). Specifically, the labels do not include the warning statement that reads, “If swallowed, get medical help or contact a Poison Control Center right away.”
Furthermore, Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL are misbranded under section 502(x) of the FD&C Act, 21 U.S.C. 352(x) because the product labels fail to disclose a complete domestic address or domestic telephone number through which the responsible person may receive a report of a serious adverse event with such drug.
In addition, SYP HEALTH HAND SANITIZER ALCOHOL GEL is packaged in a container that resembles a drinking water bottle customarily purchased by U.S. consumers. Section 502(i)(1) of the FD&C Act, 21 U.S.C. 352(i)(1), provides that a drug is misbranded if “its container is so made, formed, or filled as to be misleading …”As such, your clear, colorless hand sanitizer that fills a 33.8 fl oz container resembling a plastic water bottle ordinarily used to package drinking water is misbranded under section 502(i)(1) of the FD&C Act, 21 U.S.C. 352(i)(1).
Lastly, these products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee) because Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.
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).
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. We also recommend that the qualified consultant perform a comprehensive audit of your entire operation for CGMP compliance and that the consultant evaluates the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.
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 any 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 September 02, 2020, as the methods used in and controls used for the manufacture, processing, packing, or holding of these products do not appear to conform to current good manufacturing practices within the meaning of section 501(a)(2)(B) of the FD&C Act. Drugs and drug products that appear to be adulterated or misbranded may be detained or refused admission without physical examination.
All drugs and drug products manufactured by your firm may remain listed on this import alert, until there is evidence establishing that the conditions that gave rise to the appearance of the violation have been resolved, and the Agency has confidence that future entries will be in compliance with the FD&C Act. This may include an inspection prior to the agency considering the appearance of adulteration to be addressed.
If you decide you want to manufacture drugs for the United States in the future, request a Regulatory Meeting to discuss corrective actions.
This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot do so within 15 working days, state your reasons for delay and your schedule for completion.
Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov
Identify your response with FEI 3016833130 and ATTN: Towanda Terrell.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Registered US Agent:
Registrar Corp David Lennarz
144 Research Drive
Hampton, VA 23666
Firm’s External Attorney:
Teresa Arellano
Tere_Arellano8@hotmail.com
________________________________
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 several times, most recently on February 10, 2021. 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 substitution of hand sanitizer products declared or labeled as manufactured at your facility, a review of the purported formulations on the drug products’ labeling further indicates that these 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
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.
3
See, e.g.,
Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19)
. Because Cleaner BY CRYSTALWARE HAND SANITIZER alcohol gel and SYP HEALTH HAND SANITIZER ALCOHOL GEL are not consistent with the formulations described in these guidances, they do not fall within any temporary Agency policy not to take action against firms manufacturing hand sanitizer products for violations of section 505 of the FD&C Act.
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:
06/08/2021
Regulated Product(s)
Drugs