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Warning Letter 320-21-31

March 01, 2021

Dear Mr. Olivares:

Your firm was recently registered as a human drug manufacturer. The U.S. Food and Drug Administration (FDA) conducted testing of a consumer antiseptic hand rub drug product (also referred to as a consumer hand sanitizer) labeled as Pristine Hand Sanitizer Gel. This drug product was labeled as manufactured at your facility, Gaza Proveedora De Servicios De Hospedaje Y Alimentacion, FEI 3016808324, at Calle Castille 1473-A Colonia Jardines de la Reyna, Tonala, Jalisco, Mexico. Following an attempt to import Pristine Hand Sanitizer Gel into the United States, it was detained and refused admission at the border.

The results of FDA laboratory testing of a batch of this product detained at the border demonstrate that this drug product labeled as manufactured at your facility is adulterated within the meaning of section 501(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act or Act), 21 U.S.C. 351(c), in that its strength, purity, or quality falls below that which it purports or is represented to possess. 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 subpotency demonstrates that the quality assurance within your facility is not functioning in accordance with Current Good Manufacturing Practice (CGMP) requirements.

In addition, Pristine Hand Sanitizer Gel drug product is an unapproved new drug 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 is misbranded under sections 502(a) and (ee) of the FD&C Act, 21 U.S.C. 352(a) and (ee). Introduction or delivery for introduction of such a product 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

Pristine Hand Sanitizer Gel, labeled as manufactured at your facility, is labeled to contain 68% volume/volume (v/v) of the active ingredient alcohol ethyl alcohol (ethanol). However, FDA laboratory testing of a batch of this product detained at the border found that the drug product contained an average of only 42% v/v ethanol. This hand sanitizer drug product is adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the product lower than that which is declared on its label.

CDC recommends¹ 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 November 20, 2020, FDA held a teleconference with your registered U.S. Agent, Eport USA, LLC, but your firm did not attend. We recommended to your U.S. agent that you consider removing all of your firm’s hand sanitizer drug products currently in distribution to the U.S. market.

On November 20, 2020 FDA notified the public of the subpotency of your hand sanitizer drug product at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use.

You issued a voluntary nationwide recall of Pristine Hand Sanitizer Gel and Zapien Productos Hand Sanitizer Gel within expiry that was distributed in the U.S. market due to potential subpotency on December 01, 2020, and December 08, 2020, respectively.
In response to this letter provide the following:

• A detailed investigation into how the hand sanitizer drug product described above, which was labeled as containing 68% ethanol, in fact contained an average of 42% ethanol.
• 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 subpotency of hand sanitizer drug products 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.²

Unapproved New Drug and Misbranding Violations

Pristine Hand Sanitizer Gel is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is 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 it is intended to affect the structure or any function of the body. Specifically, this product is intended for use as a consumer topical antiseptic.

Examples of claims observed on the Pristine 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 . . . DRUG FACTS . . . Purpose: Antiseptic . . . Uses: Helps reduce bacteria on skin. . . Wet hands thoroughly with product and allow to dry without wiping.”

This topical antiseptic product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its 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 this product, 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 this product, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your Pristine Hand Sanitizer Gel drug product is GRASE for use under the conditions suggested, recommended, or prescribed in its labeling. Accordingly, this product is an unapproved new drug 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 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, Pristine Hand Sanitizer Gel does not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rub proposed rule, nor any other TFM, proposed rule, or final rule, and does 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 label, Pristine Hand Sanitizer Gel purportedly contains the active ingredient ethyl alcohol (ethanol) 68% v/v. However, as previously discussed, FDA laboratory analysis of a batch of this product detained at the border demonstrated that Pristine Hand Sanitizer Gel contains ethanol in a concentration of ethanol that is less than the 68% v/v declared on the label and less than the amount of ethanol described in the 1994 TFM.³ Such a product does not conform with the TFM and other applicable requirements, nor is it 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

Additionally, this hand sanitizer is misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), because its labeling is false or misleading. As noted above, Pristine Hand Sanitizer Gel is labeled to contain ethanol 68% v/v. However, FDA laboratory analysis of a sample from a batch of this product demonstrates that the product contains concentrations of ethanol that are far less than that stated on its product label. Thus, the misleading representations of the concentration of the active ingredient ethanol on the Pristine Hand Sanitizer Gel labeling cause this product to be misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).

Lastly, this product is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee) because Pristine Hand Sanitizer Gel is a nonprescription drug subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but does not comply with the requirements for marketing under that section and is 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 December 22, 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. 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 [email protected]

Please identify your response with FEI 3016808324 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:
Eport USA LLC
Veronica Ortiz de Montellano
6200 Savoy Dr.
Houston, TX 77036

______________________________

1 https://www.cdc.gov/handwashing/hand-sanitizer-use.html

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 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 a 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 subpotency of hand sanitizer products labeled as manufactured at your facility, a review of the drug products’ labeling further indicates that this product is not prepared consistent with FDA’s temporary policy set forth in the guidance. Therefore, this product does 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 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 See, e.g., Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19). Because Pristine Hand Sanitizer Gel is not consistent with the formulations described in these guidances, it does 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.