WARNING LETTER
EnviroServe Chemicals & Cleaners Ltd.
MARCS-CMS 674090 —
September 09, 2024
Delivery Method:
VIA UPS
Product:
Drugs
Recipient:
Recipient Name
Mr. H. Arthur Matossian
Recipient Title
President
EnviroServe Chemicals & Cleaners Ltd.
110 Ronson Drive
Etobicoke
ON
M9W 1B6
Canada
Issuing Office:
Center for Drug Evaluation and Research (CDER)
United States
Warning Letter 320-24-60
September 9, 2024
Dear Mr. Matossian:
Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our June 16, 2022 request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, EnviroServe Chemicals & Cleaners Ltd., FEI 3011214285, at 110 Ronson Drive, Etobicoke, Ontario M9W 1B6, Canada.
This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request do not conform to CGMP, your drug 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 addition, SOPURE ANTISEPTIC SKIN CLEANSER 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), 502(c), and 502(ee) of the FD&C Act, 21 U.S.C. 352(a), 352(c), and 352(ee). Introduction or delivery for introduction of such products into interstate commerce is prohibited under sections 301(d) and 301(a) of the FD&C Act, 21 U.S.C. 331(d) and 331(a). These violations are described in more detail below.
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:
CGMP Violations
1. 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) & 211.84(d)(2)).
Your firm manufactured over-the-counter (OTC) drug products including SOPURE ANTISEPTIC SKIN CLEANSER hand sanitizer.
1
Based on the records and information you provided, you did not demonstrate that you are adequately testing the identity of incoming components used in the manufacture of your drug products. You also did not demonstrate that you are testing your active ingredient ethanol for methanol.
Without adequate testing and establishing the reliability of your component suppliers’ test analyses at appropriate intervals, you do not have scientific evidence that your raw materials conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality, including testing for the presence of methanol in ethanol.
The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document,
Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol
, at https://www.fda.gov/media/173005/download.
2. 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)).
Based on the records and information you provided, you did not demonstrate that you conducted adequate finished drug product testing on your drug products. For example, the SOPURE ANTISEPTIC SKIN CLEANSER hand sanitizer batch records that you provided, do not include an appropriate assay test for active ingredient content or adequate impurity testing. Your firm conducts alcohol content testing by measuring density using hydrometer equipment, and tests for methanol and
(b)(4)
through organoleptic inspection for odor.
Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that your drug products conform to appropriate specifications before release.
3. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).
Based on the records and information you provided, you failed to provide adequate stability data to demonstrate that the chemical properties of your SOPURE ANTISEPTIC SKIN CLEANSER hand sanitizers remain acceptable throughout the labeled expiry period. For example, you provided long-term stability studies and reported that the expiry period assigned and applied to your hand sanitizer product is
(b)(4)
. However, your stability data does not include adequate testing for identity and strength. Your firm conducts alcohol content testing by measuring density using hydrometer equipment, and tests for methanol and
(b)(4)
through organoleptic inspection for odor. Therefore, the data does not demonstrate that the drug’s active ingredient is stable throughout its shelf life.
Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their
labeled expiry.
4. 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 provided demonstrate that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your drug manufacturing operations.
Your QU is responsible for fully exercising its authority and responsibilities. FDA is concerned that your QU may not be conducting appropriate oversight regarding CGMP operations.
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 CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.
Unapproved New Drug Violations
Based on its labeled intended uses, SOPURE ANTISEPTIC SKIN CLEANSER 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 topical consumer antiseptic rub.
Examples of claims observed on the SOPURE ANTISEPTIC SKIN CLEANSER 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:
“Kills harmful bacteria/germs . . .
Drug Facts . . . Use(s)
. . . Kills harmful bacteria/germs” [from product label]
“EFFECTIVE AGAINST KILLING BACTERIA, VIRUSES, AND GERMS . . . EFFECTIVELY CLEAN AND DISINFECT SURFACES AND HANDS IN ONE STEP” [from your product website: https://sopureproducts.ca]
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) 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 this drug product, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your SOPURE ANTISEPTIC SKIN CLEANSER 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).
Over-the-Counter (OTC) topical and oral antiseptic products have been the subject of rulemakings under the Agency’s OTC Drug Review. In particular, consumer topical antiseptics 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. Even if your product were marketed as an antiseptic wash rather than a rub, we note that 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 governs 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, SOPURE ANTISEPTIC SKIN CLEANSER does not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rule and the Consumer Antiseptic Washes proposed rule, nor any other TFM, proposed rule, or final rule, and does not meet the conditions under sections 505G(a)(1) or 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505.
For example, your SOPURE ANTISEPTIC SKIN CLEANSER includes the label claim, “EFFECTIVE AGAINST KILLING…VIRUSES.” The monograph conditions of use for OTC antiseptic rub products as set forth in the rulemakings described above limit the use of the product to help reduce bacteria that potentially can cause disease. Therefore, your product does not conform to the TFM or the applicable requirements and goes beyond describing the intended use of topical antiseptics as set forth in the 1994 TFM and amended by the 2016 Consumer Antiseptic Rubs Proposed Rule
2
.
This intended use claim is inconsistent with the applicable TFMs or any other TFM or proposed rule, and accordingly does not meet the conditions under sections 505G(a)(1) or 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505.
Misbranded Drug Violations
In addition, SOPURE ANTISEPTIC SKIN CLEANSER is misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), because the acronym “FDA,” in a form that is similar to the FDA logo and “U.S. FOOD & DRUG ADMINISTRATION,” is displayed on your website along with the statement, “. . . our hand sanitizer meets the highest standards of quality and safety, as confirmed by . . . FDA (80773-001) registrations.” FDA’s regulations provide that “[r]egistration of an establishment or listing of a drug does not denote approval of the establishment, the drug, or other drugs of the establishment, nor does it mean that a product may be legally marketed. Any representation that creates an impression of official approval or that a drug is approved or is legally marketable because of registration or listing is misleading and constitutes misbranding” (21 CFR 207.77(a)). The assertion that your products “meet the highest standards of quality and safety,” combined with your website’s use of the acronym FDA in a form that is similar to the FDA logo, misleadingly suggests that the drug product is approved or endorsed by FDA in some way. As previously noted, your SOPURE ANTISEPTIC SKIN CLEANSER product is not the subject of an FDA-approved application. Labeling with a representation suggesting that this product is FDA-approved is false or misleading, causing the drug to be misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).
SOPURE ANTISEPTIC SKIN CLEANSER is also misbranded under section 502(c) of the FD&C Act, 21 U.S.C. 352(c), because the product’s Drug Facts panel contains extraneous information that goes beyond the required directions described in the rulemakings mentioned above. Specifically, 21 CFR 201.66(d)(7) states that additional information not described in the content requirements for OTC drug products should not appear in the Drug Facts panel. However, the Uses section for your product’s Drug Facts panel includes language such as “Medical skin cleanser” that is not consistent with the uses provided for in the applicable rulemakings for consumer antiseptic rubs and consumer antiseptic washes.
Lastly, SOPURE ANTISEPTIC SKIN CLEANSER is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because it 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.
Introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).
CGMP Consultant Recommended
If your firm intends to resume manufacturing drugs for the U.S. market, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements before resuming drug manufacturing operations. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPAs before you pursue resolution of your firm’s compliance status.
Conclusion
The violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.
FDA placed your firm on Import Alert 66-40 on April 1, 2024.
Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may inspect to verify that you have completed corrective actions to any violations.
Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at EnviroServe Chemicals & Cleaners Ltd., at 110 Ronson Drive, Etobicoke, Ontario M9W 1B6, Canada, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated or misbranded may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
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 complete corrective actions 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 3011214285 and ATTN: LaKeesha M. Sifontes.
Sincerely,
/S/
Francis Godwin
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
CC:
Registered U.S. Agent
Mr. Abul Ansari
3729 Shires Edge Drive
New Hill, NC 27562-9341
_____________________
1
Due to an increased demand for alcohol-based hand sanitizers during the COVID-19 pandemic, the 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. This guidance communicated the Agency’s temporary policy that we did not intend to take action against firms for CGMP violations under section 501(a)(2)(B) of the FD&C Act if such firms prepared 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 were present. These circumstances included preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. The guidance was withdrawn effective December 31, 2021 (86 Fed Reg at 56960). Because EnviroServe Chemicals & Cleaners, Ltd., hand sanitizer products were not prepared under the circumstances described in this guidance, they do not fall within any temporary agency 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 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.
Content current as of:
09/17/2024
Regulated Product(s)
Drugs