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Warning Letter 320-21-58

September 15, 2021

Dear Mr. Gutiérrez:

Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products, including consumer antiseptic rub drug products (also referred to as a consumer hand sanitizer).

The FDA conducted testing of a product, labeled as ZANILAST + Gel, 25 kg. This drug product was labeled as manufactured at your facility. Following an attempt to import ZANILAST + Gel, 25kg into the United States, it was detained and refused admission at the border.

The results of the 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(d)(2) of the FD&C Act, 21 U.S.C. 351(d)(2), in that a substance was substituted wholly or in part therefor.

Additionally, FDA has reviewed the records you submitted in response to our initial April 22, 2020, request for records and other information, and subsequent correspondence, pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Nanomateriales Químicos Avanzados, S.A. de C.V., formerly known as Nanomateriales S.A. de C.V., FEI 3010525809, at Av. Milimex 215, Col. Parque Industrial Milimex, Apodaca, Nuevo Leon 66637, Mexico.

Based on information provided in response to our 704(a)(4) request and the substitution determined by FDA laboratory testing, the methods used in, or the facilities or controls used for, the manufacture, processing, packing, or holding of drugs do not conform to current good manufacturing practice (CGMP) within the meaning of section 501(a)(2)(B) of the FD&C Act.

This warning letter also summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

In addition, in response to our 704(a)(4) request you provided a copy of the label for ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon. Our review of the label has determined that ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon is an unapproved new drug in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Additionally, ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). 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).

ZANILAST + GEL 25kg is misbranded under sections 502(f)(1), (a), (e)(1)(A), (c), and (x) of the FD&C Act, 21 U.S.C. 352(f)(1), (a), (e)(1)(A), (c), and (x). Introduction or delivery for introduction of such products into interstate commerce is prohibited under sections 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.

Adulteration Violations

ZANILAST + Gel, 25kg bulk labeled as manufactured at your facility, is labeled to contain 65% 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 an average 0.0% ethanol and an average of 41% 1-propanol volume/volume (v/v). 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 1-propanol, a dangerous chemical when in contact with human skin or ingested.

1-propanol, not to be confused with isopropyl alcohol or 2-propanol, is not a permitted active ingredient in hand sanitizers intended for the United States. Exposure to 1-propanol may cause irritation to eyes, nose; throat; dry cracking skin; drowsiness, headache; ataxia, gastrointestinal pain; abdominal cramps, nausea, vomiting and diarrhea. Although all persons using these products on their hands are at risk, young children who accidentally ingest these products, and adolescents and persons with alcohol addiction who drink these products as an alcohol (ethanol) substitute, are most at risk for 1-propanol poisoning.

On August 17, 2020, FDA held a teleconference with you. We recommended you consider removing all of your firm’s hand sanitizer drug products currently in distribution to the U.S. market. On August 17, 2020, FDA notified the public of the 1-propanol contamination substitution of your hand sanitizer drugs products at the following website:
https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use

On August 26, 2020, you issued a voluntary nationwide recall of ZANILAST + Gel Hand Sanitizer because of the potential presence of undeclared 1-propanol, as noted on the following FDA website:
https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/nanomateriales-sa-de-cv-issues-voluntary-nationwide-recall-all-lots-zanilastgel-due-presence-1

In response to this letter, provide the following:
• A list of all raw materials used to manufacture all 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 United States.
• Summary of corrective actions taken to ensure your hand sanitizer products can be manufactured at the label claim concentration of 65% v/v ethanol.
• Details regarding your raw material identity testing of incoming active pharmaceutical ingredients and specifically how your test methods can distinguish between ethanol and 1-propanol.
• Provide a complete, comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.

The substitution and contamination with 1-propanol in a drug product 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.¹

21 CFR parts 210 and 211 Violations

Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:

1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).

Your response to our records request and other information under section 704(a)(4) indicated that you did not conduct adequate finished drug product testing on drug products shipped to the United States.

Specifically, in response to our 704(a)(4) request for all finished product specifications and test methods used to evaluate them, you referenced an operational manual which stated that your hand sanitizer is only tested for pH, viscosity, density, and appearance and provided stability data for one batch in which only pH and viscosity were evaluated. In a subsequent response on September 5, 2020, you provided a procedure which stated that finished product must be tested according to its specifications before release, but you did not provide revised specifications for your hand sanitizer drug product. The documents you provided in response to our 704(a)(4) request indicate that you do not perform identity, assay, or purity testing of the active ingredient in your finished drug product. Full release testing including strength and identity testing of the active ingredient must be performed before drug release and distribution.

In response to this letter, provide the following:

• A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision. Specify which tests are performed by your facility and which if any are performed by a contract testing laboratory.
  o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing reserve samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
• Ethanol and 1-propanol test results for all batches of hand sanitizer shipped to the United States within expiry.

2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and (2)).

Based on the records and information you provided, you did not demonstrate adequate identity testing of incoming components used to manufacture your drug products, and you accepted test results from suppliers without verifying information provided by suppliers. We requested details about your raw material identity testing for each lot of each component and you stated that material test results are accepted from the supplier’s Certificate of Analysis (COA). We asked again on August 25, 2020, and you stated that COA values are accepted from “reliable” suppliers. There is no evidence that you perform identity testing on each lot of incoming components.

For your component suppliers, we requested the last date of supplier qualification, audit frequency, and the last three audit dates as applicable. You replied only that you did not have an audit frequency. We asked for supplier qualification information again on August 25, 2020, and you provided a procedure created July 3, 2020, describing the evaluation and selection of suppliers. However, this procedure does not provide any specific guidance on evaluating the quality of a supplier or the validity of data listed on a supplier’s COAs.

In response to this letter, provide the following:

• The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.
• A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COAs instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.
• A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.
• A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
• A comprehensive review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.

3. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a))

The records and information you submitted demonstrate that your quality unit (QU) lacks adequate quality oversight over the manufacture and release of finished drug product shipped to the United States.

Specifically, your drug substance supplier provided incorrect information that 1-propanol was an allowable active ingredient in hand sanitizer intended for use in the United States. You accepted this information and altered your drug product formula without evaluating the impact of this change on product quality. Subsequently, you released hand sanitizer batches (b)(4) which contained 1-propanol as the active ingredient. On September 9, 2020, we requested the labels for these batches. You provided these labels which declare “65.00% alcohol” and “70% ethyl alcohol” content respectively, demonstrating that your QU released mislabeled material.

As of your September 10, 2020, response, you understood that 1-propanol is an unacceptable active ingredient in hand sanitizer, committed to test for 1-propanol in your future finished hand sanitizer products, and will no longer use that drug substance supplier. However, your response lacked documentation and sufficient detail to demonstrate that you are establishing appropriate operational programs, systems, and related procedures to ensure product quality, such as those responsible for manufacturing changes. You also failed to address the potential impact that your lack of quality oversight had on the quality of all drugs that you manufacture.

Your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality. See FDA's guidance document, Quality Systems Approach to Pharmaceutical CGMP Regulations, for help implementing quality systems and risk management approaches to meet the requirements of the CGMP regulations (21 CFR, parts 210 and 211) at: https://www.fda.gov/media/71023/download.

In response to this letter, provide the following:

• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:
  o A determination of whether procedures used by your firm are robust and appropriate
  o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
  o A complete and final review of each batch and its related information before the QU disposition decision
  o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
• A comprehensive assessment of your change management system. This assessment should include, but not be limited to, your procedure(s) to ensure changes are justified, reviewed, and approved by your QU. Your change management program should also include provisions for determining change effectiveness.

Unapproved New Drug and Misbranding Violations

ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon and ZANILAST + GEL, 25kg 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, these products are intended for use as a consumer topical antiseptic.

Examples of claims observed on the ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon product label and labeling 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:

“ANTISPETIC HAND SANITIZER . . . Drug Facts…Antiseptic…Use…For hand washing to decrease bacteria on the skin”

“wet hands thoroughly with product and allow to dry without wiping”²
Documents you submitted in support of your August 2020 import entry for ZANILAST + GEL, 25kg including a product list, provide evidence of the product’s intended use (as defined in 21 CFR 201.128) as a hand sanitizer drug product. Further, examples of claims observed on the ZANILAST + GEL, 25kg 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:

Product Label:

“ZANILAST + GEL is a stabilized compound that contains 70% of ethanol. In order to maximize its biocidal power, a compound based on zinc oxide is added.”

“…formulated with broad-spectrum sanitizing agents, obtained by an advanced physicochemical process that gives it an ideal composition and particle size to guarantee a broad biocidal power against bacteria, fungi, and viruses.”

Accordingly, your firm’s ZANILAST + GEL, 25kg is a drug within the meaning of section 201(g)(1)(D) of the FD&C Act.

ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon 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 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 it is lawfully marketed under section 505G of the FD&C Act (which is not the case for this product, as further described below) or 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 ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon drug product is GRASE for use under the conditions suggested, recommended, or prescribed in its labeling. Accordingly, ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon 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 OTC topical antiseptic products had been the subject of rulemaking under the Agency’s 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 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.

Additionally, OTC consumer antiseptic washes were addressed in “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use,” Proposed Rule, 78 FR 76444 (December 17, 2013) (Consumer Antiseptic Washes Proposed Rule) and “OTC Safety and Effectiveness of Topical Antimicrobial Drug Products for Over-the-Counter Human Use,” Final Rule, 81 FR 61106 (September 6, 2016). We note that ethyl alcohol is not one of the active ingredients that was classified as Category III for use as an active ingredient in a consumer antiseptic wash. Under the Consumer Antiseptic Washes rulemaking, ethyl alcohol was determined to be ineligible for evaluation under the OTC Drug Review for use as an active ingredient in consumer antiseptic washes.

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 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, ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon does not confirm to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rule and 2013 Consumer Antiseptic Washes 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.

As previously noted, statements on the ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon label suggest both that the product is a consumer antiseptic wash and a consumer antiseptic rub. However, ethanol (in any concentration) is not an active ingredient permitted for use in consumer antiseptic hand wash under the 1994 TFM. Moreover, antiseptic washes are outside the scope of FDA’s temporary policies for hand sanitizers.

The introduction or delivery for introduction of an unapproved new drug into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d).

ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because ZANILAST + GEL ANTISEPTIC HAND SANITIZER, 1 gallon 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 it is not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.

Furthermore, ZANILAST + GEL is misbranded under section 502(f)(1) of the FD&C Act, 21 U.S.C. 352(f)(1), because its labeling fails to bear adequate directions for use. Specifically, ZANILAST + GEL’s labeling does not contain sufficient information to enable laypersons to use the product safely and for the purposes for which it is intended, including frequency of administration, duration of administration, time of administration, route or method of administration, and preparation for use.³

In addition, ZANILAST + GEL is misbranded under section 502(a) of the FD&C Act, 21 U.S.C 352(a), because its labeling is false or misleading. ZANILAST + GEL is labeled to contain ethanol 65% and 70%. Such a representation by itself is misleading. However, FDA laboratory analysis of a batch of this product demonstrate that the product contains no traceable amount of ethanol and contains a significant concentration of 1-propanol, 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 1-propanol 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 ZANILAST + GEL drug product to list 1-propanol 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).

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).

Additional Concerns

We note that according to the product label, ZANILAST + GEL purportedly contains the active ingredient ethyl alcohol at both 65% and 70% v/v, However, as previously discussed, FDA laboratory analyses of a batch of this product detained at the border demonstrated that ZANILAST + GEL contains no traceable amount of ethanol. Such a product does not conform with 1994 TFM or the 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

FDA laboratory analyses also demonstrated that a batch of ZANILAST + GEL contain significant concentrations of undeclared ingredient1-propanol. Use of 1-propanol as an active ingredient is not in conformance with the 1994 TFM, nor is 1-propanol 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, the product is labeled with alcohol, water, glycerin D-limonene, triethanolamine, carbomer, zinc oxide, and zinc pyrithione as active ingredients.⁵ Neither water, glycerin D-limonene, triethanolamine, carbomer, zinc oxide, nor zinc pyrithione are permitted active ingredients, as a sole ingredient or in combination with other ingredients like ethanol, for use as a consumer or health care personnel antiseptic rub drug products. Such a product is not permitted under the TFM or 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.⁶

In addition, the labeling of ZANILAST + GEL indicates that it provides ”biocidal power” against fungi and viruses. These labeled intended uses go beyond merely describing the general intended use of a topical antiseptic as set forth in the 1994 TFM, as amended by the 2016 proposed rule, and FDA’s before-noted temporary policy.⁷

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 31, 2020, and Import Alert 66-40 on January 12, 2021, 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 pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3).

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 FD&C Act. This may include an inspection prior to the Agency considering the appearance of adulteration to be addressed.

Until all violations are addressed completely, and we confirm your compliance with CGMP, they may be cause for FDA to withhold approval of any new drug applications or supplements listing your firm as a drug manufacturer.

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].

Identify your response with FEI 3010525809 and ATTN: Christina Capacci-Daniel.

Sincerely,
/S/

Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research

CC:
Registered U.S. Agent:
David Lennarz
Register Corp
144 Research Drive
Hampton, VA, 23666
757-224-0177
[email protected]

_________________________

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 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 substitution of hand sanitizer products labeled as manufactured at your facility, a review of the purported formulations on the drug products’ labeling further indicates 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 We note that your ZANILAST + GEL ANTISEPTIC HAND SANITIZER labeling contains conflicting information regarding whether it should be used as a consumer antiseptic wash or a consumer antiseptic rub. The term “hand sanitizer” generally refers to consumer antiseptic rubs, and the Drug Facts Label of your product both indicates that the product is to be used for handwashing (presumably with water) and suggests that it should be used without water (i.e., “wet hands thoroughly with product and allow to dry without wiping”). The ZANILAST + GEL ANTISEPTIC HAND SANITIZER product, however, does not conform to the requirements for either a consumer antiseptic rub or a consumer antiseptic wash, as further described below.

3 We note that you include the statement, "Caution: For manufacturing, processing, or repacking,” on your product label, perhaps in an attempt to claim the exemption from section 502(f)(1) under 21 CFR 201.122. However, to the extent that 21 CFR 201.122 applies, ZANILAST + GEL cannot claim the exemption because it is a substance intended for a use in manufacture, processing, or repacking which causes the finished article to be a new drug, and does not meet any of the conditions set forth in 21 CFR 201.122(a)-(c).

4 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 denatured in accordance with Bureau of Alcohol, Tobacco and Firearms regulations. 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.

5 The labeling and formulation for ZANILAST + GEL is not consistent with the conditions proposed for OTC hand sanitizers (i.e., antiseptic rub) for consumer and/or health care personnel use under the 1994 TFM (see 59 FR 31402; June 17, 1994), as further amended by subsequent proposed rules. Specifically, the label for ZANILAST + GEL does not distinguish active ingredients from inactive ingredients. Therefore, all of the labeled ingredients (alcohol, water, glycerin D-limonene, triethanolamine, carbomer, zinc oxide, and zinc pyrithione) are deemed to be represented as active ingredients, see 21 CFR 201.66(b)(2).

6 See, e.g., Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19).

7 The 1994 TFM covers health care antiseptics that are indicated for use to help reduce bacteria that potentially can cause disease and health care and consumer antiseptics that are indicated for use to decrease bacteria on the skin. 59 FR at 31443.