WARNING LETTER
Grupo Plast-Y-Kosas, SA de CV
MARCS-CMS 609493 —
January 25, 2021
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
Mr. Wenceslao Garcia
Recipient Title
Owner
Grupo Plast-Y-Kosas, SA de CV
Callejon Puebla 105-Co
Col. Rodriguez
88630
Reynosa
,
Tamps.
Mexico
Issuing Office:
Center for Drug Evaluation and Research | CDER
United States
Warning Letter 320-21-18
January 25, 2021
Dear Mr. Garcia:
Your firm was registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of consumer antiseptic rub drug products (also referred to as a consumer hand sanitizer) labeled asM HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER, and O.K. PHARMACY HAND SANITIZER. These drug products were labeled as manufactured at your facility, Grupo Plast-Y-Kosas SA de CV, FEI 3016756400, at Callejon Puebla 105, Reynosa, Tamaulipas, Mexico. Following an attempt to import M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER, and O.K. PHARMACY HAND SANITIZER into the United States, they were detained and refused admission at the border.
The results of the FDA laboratory testing of a batch ofM HAND SANITIZER drug product detained at the border demonstrate that this drug product labeled as manufactured at your facility is adulterated within the meaning of section 501(d)(2) of the Federal Food, Drug, and Cosmetic Act (FD&C Act or the Act), 21 U.S.C. 351(d)(2), in that a substance was substituted wholly or in part therefor. In addition, this product is 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.
The results of the FDA laboratory testing of batches of Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER drug products detained at the border demonstrate that these drug products are adulterated within the meaning of section 501(c) of the FD&C Act, 21 U.S.C. 351(c), in that their strength, purity, or quality falls below that which they purport or are represented to possess. 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 subpotency demonstrates that the quality assurance within your facility is not functioning in accordance with CGMP requirements.
In addition, M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER, and O.K. PHARMACY HAND SANITIZER 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(a) and (ee) of the FD&C Act, 21 U.S.C. 352(a) and (ee). Additionally, M HAND SANITIZER is misbranded under sections 502(j) and (e) of the FD&C Act, 21 U.S.C. 352(j) and (e). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 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
M HAND SANITIZER, labeled as being manufactured at your facility, is labeled to contain 80% volume/volume (v/v) of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this drug product detained at the border found that the drug product contained an average of 0.87% ethanol v/v and 15% methanol v/v. Therefore, this hand sanitizer drug product is adulterated under section 501(d)(2) of the FD&C Act in that the active ingredient, 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.
Jalisco Paper Inc. HAND SANITIZER, labeled as manufactured at your facility, is labeled to contain 80% v/v of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug product contained only 8.6% ethanol v/v. Additionally, O.K. PHARMACY HAND SANITIZER, labeled as manufactured at your facility, is labeled to contain 80% v/v of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug product contained only 9.2% ethanol v/v. These hand sanitizer drug products are adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the products lower than that which is declared on their labeling.
CDC recommends that, if soap and water are not readily available, consumers use an alcohol-based hand sanitizer that contains not less than 60% alcohol (ethanol). This is the minimum active ingredient concentration of ethanol specified in the 1994 Tentative Final Monograph for Health-Care Antiseptic Drug Products (59 FR 31402), 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).
On August 11, 2020, FDA notified the public of the methanol contamination of your drugs at the following website:
https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
.
On August 20, 2020, FDA held a teleconference with your counsel, Davidson Law Group, P.A. which stated that it represents both you and your registered US Agent,
1
MEDEK LLC. We recommended to your counsel that you consider removing all of your firm’s hand sanitizer drug products currently in distribution to the U.S. market. On September 9, 2020, you issued a voluntary nationwide recall of M HAND SANITIZER 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/medek-llc-issues-voluntary-nationwide-recall-m-hand-sanitizer-due-potential-presence-methanol-wood
.
In response to this letter provide the following:
• A detailed investigation into how the M HAND SANITIZER drug product, which was manufactured at your facility, and which was labeled as containing alcohol (ethanol), was substituted in part or in whole with methanol.
• A detailed investigation into how the Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER drug products you manufactured, and labeled as containing 80% alcohol (ethanol), in fact contained 8.6% and 9.2% ethanol, respectively.
• 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 contamination with methanol and the subpotency of hand sanitizer drug products labeled as manufactured in your facility demonstrate 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.
2
Unapproved New Drug and Misbranding Violations
M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER, and O.K. PHARMACY HAND SANITIZER 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 use in 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, M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER are intended for use as consumer topical antiseptics.
Examples of claims observed on the M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER, and O.K. PHARMACY HAND SANITIZER product labels and 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:
Drug Facts…Uses…Hand Sanitizer to help reduce bacteria that potentially can cause disease. For use when soap and water are not available.
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 FD&C Act (which is not the case for these products, as further described below). 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 M HAND SANITIZER , Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER 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 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 “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 as 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 antiseptic 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, M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER Alcohol Free do not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rule, 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 their product labels, M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER purportedly contain the active ingredient ethyl alcohol (ethanol) 80% v/v. However, as previously discussed, FDA laboratory analyses of batches of these products detained at the border demonstrate that M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER contain ethanol in a concentration that is less than the 80% v/v stated on their product labels and less than the amount of ethanol described in the 1994 TFM. Such products do not conform with the TFM or the applicable requirements,
3
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.
4
FDA laboratory analyses also demonstrate that a batch of M HAND SANITIZER contains 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 a product’s inactive ingredients be safe and suitable.
5
Additionally, this methanol-containing drug product, M HAND SANITIZER, is misbranded under sections 502(j), (a), (e), and (ee) of the FD&C Act, 21 U.S.C. 352(j), (a), (e), and (ee). It is misbranded under section 502(j) of the FD&C Act, 21 U.S.C. 352(j), because it is dangerous to health when used according to its labeling as a hand sanitizer. 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. M HAND SANITIZER is misbranded under section 502(a) of the FD&C Act, 21 U.S.C 352(a), because its labeling is false and misleading. As noted above, M HAND SANITIZER is labeled to contain ethyl alcohol (ethanol) 80% v/v. However, FDA laboratory analyses demonstrate that a batch of this product contains a concentration of ethyl alcohol (ethanol) that is far less than what is stated on the product label and contains a significant concentration of methyl alcohol (methanol), an ingredient that is not declared on the product label. 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 label to disclose the presence of the methyl alcohol (methanol) in the product, causes this product to be misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). The failure of M HAND SANITIZER to list methanol as an ingredient on its label also causes it to be misbranded under section 502(e)(1)(A) of the FD&C Act, 21 U.S.C. 352(e)(1)(A).
Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER 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, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER are labeled to contain ethyl alcohol (ethanol) 80%. However, FDA laboratory analyses revealed that batches of these products contain concentrations of ethanol that are far less than that stated on their respective product labels.
Lastly, M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee) because they are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but they 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 August 11, 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 a violation have been resolved, and the Agency has confidence that future entries will be in compliance with the 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. 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.go
Identify your response with FEI 3016756400 and ATTN: Michael Klapal
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Registered US Agent:
Dennis Garcia, Owner
MEDEK LLC
315 E Business Highway 83
Alamo, TX 78516-9627
Regulatory Counsel:
Scott J. Davidson
Davidson Law Group, P.A.
7950 NW 53rd Street
Suite 337
Miami, FL 33166
________________________________
1
Under section 510(i)(1) of the FD&C Act, 21 U.S.C. 360(i)(1), you are required to submit registration information annually by electronic means for each foreign establishment you own or operate engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is imported or offered for import into the United States, and include the name of the United States Agent. On May 12, 2020, the registration for Grupo Plast Y Kosas identified Medek (DUNS 055524072) as the U.S. Agent. As a drug manufacturer, it is your responsibility to ensure complete and accurate registration information.
2
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 August 7, 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 rub) 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 and subpotency of hand sanitizer products declared or labeled as manufactured at your facility, FDA laboratory examination of the O.K. PHARMACY HAND SANITIZER found it to be a gel-like liquid which indicates undeclared ingredients were used in its manufacture and consequently it was 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.
3
The 1994 TFM, which does not distinguish between antiseptic hand washes and rubs, proposed for antiseptic hand washes and healthcare personnel hand washes an alcohol concentration of 60 to 95% by volume in an aqueous solution: 59 FR 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
See, e.g., Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19). Because M HAND SANITIZER, Jalisco Paper Inc. HAND SANITIZER and O.K. PHARMACY HAND SANITIZER are not consistent with the formulations 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.
5
An inactive ingredient used in 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:
01/26/2021
Regulated Product(s)
Drugs