- Delivery Method:
- VIA UPS
Recipient NameMr. Tony Geng
Recipient TitleOwner and President
- Superior Glove Works, Ltd.
Acton ON L7J 1S1
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
Warning Letter 320-23-09
December 16, 2022
Dear Mr. Geng:
Your facility was registered with the United States Food and Drug Administration (FDA or Agency) as a manufacturer of over-the-counter (OTC) drug products, including consumer antiseptic hand rub drug products (also referred to as consumer hand sanitizers), until August 25, 2022. FDA has reviewed the records you submitted in response to our October 19, 2021, request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 374(a)(4)) for your facility, Superior Glove Works, Ltd., FEI 3006217765, at 36 Vimy St., Acton, Ontario.
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 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))1.
Synergy Hand Sanitizer (HS) Alcohol Antiseptic 80% Topical Solution and Synergy Hand Sanitizer with Aloe (HSA) Alcohol Antiseptic 70 % Topical Solution were manufactured at your facility. One of the supplier’s Certificates of Analysis (COA) you provided in response to our 704(a)(4) request for records and other information demonstrates that ethanol API used to manufacture your drug products in U.S. distribution contained impurities at unacceptable levels. Acetaldehyde impurities were found to be 205 parts per million (ppm) and the sum of all impurities were found to be 2,846 ppm.
Acetaldehyde appears to be genotoxic, and potentially carcinogenic, when in direct contact with tissues.
On August 30, 2022, FDA held a teleconference with you. We recommended you consider removing any batches of Synergy Hand Sanitizer (HS) Alcohol Antiseptic 80% Topical Solution drug product currently in distribution from the U.S. market which may have been manufactured using the ethanol API that contained impurities at unacceptable levels.
On September 1, 2022, you issued a voluntary nationwide recall of one batch of Synergy Hand Sanitizer (HS) Alcohol Antiseptic 80% Topical Solution due to the presence of acetaldehyde impurities and the sum of all impurities at unacceptable levels.
The contamination with acetaldehyde and other unidentified impurities in the drug product manufactured in your facility, in addition to the significant violations observed in the 704(a)(4) record request, 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.
704(a)(4) Request for Records and Related CGMP 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 conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).
Your response to our request for records and other information under section 704(a)(4) indicated that you did not adequately test incoming components used in the manufacture of your drug products before release and distribution to the United States. Specifically, in response to our request to provide details about your raw material incoming and identity testing for each lot of each component of the API for your hand sanitizer you state that you “do not test methanol content in incoming ethanol”, you do not perform identity testing of raw materials, and that “incoming materials are required to be accompanied by COA”.
You further indicated in your response that you used (b)(4) suppliers of ethanol API to manufacture your hand sanitizer drug products. However, no impurity testing specifications (benzene, methanol, acetal, acetaldehyde, etc.) were listed on COAs from (b)(4) of your ethanol API suppliers, and the COA from a (b)(4) supplier had impurity levels (acetaldehyde 900ppm max and sum of all impurities 5000ppm max) that were above acceptable levels. Acetaldehyde and acetal are known impurities of alcohol, as delineated in the United States Pharmacopeia (USP). The USP monograph for alcohol limits acetaldehyde and acetal to not more than (NMT) 10mL/L, 10 ppm (expressed as acetaldehyde). Alcohol not meeting the specification for acetaldehyde and acetal is deemed adulterated under section 501(b) of the FD&C Act. Alcohol represents a significant component of your drug product; therefore, you must have a specification for acetaldehyde and acetal per 21 CFR 211.160(b).
Component testing is fundamental to quality. Without adequate testing, you do not have scientific evidence that your raw materials conform to appropriate specifications before use in the manufacture of your drug products.
In response to this letter, provide:
- A comprehensive, independent 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.
- 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 COA 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 standard operating procedure (SOP) that describes this COA validation program.
- The chemical and microbiological quality control specifications you use to test and release each incoming lot of components for use in manufacturing.
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 adequately test your finished OTC drug products prior to release, including over 90 shipments of hand sanitizer drug products distributed to the United States, as there is no indication that you test for known impurities present in your raw materials. For example, we requested that you provide the test results of all finished batches of hand sanitizer that had been shipped to or distributed in the United States. The records you provided in your response indicated that you have only performed limited release testing as part of the production record (viscosity for HSA drug products and final potency of alcohol content for both HS and HSA drug products).
Full release testing, including for identity, strength, and impurities, must be performed prior to drug release and distribution. Without adequate testing, there is no scientific evidence to assure that your drug products conform to appropriate specifications before release.
In response to this letter, provide:
- A list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a disposition decision:
o An action plan and timelines for conducting full chemical and microbiological testing of reserve 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.
- A 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.
3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).
Based on the information you provided, you did not demonstrate that your manufacturing processes are reproducible and controlled to yield a product of uniform character and quality. For example, your batch records did not include any process parameters or in-process specifications to demonstrate control in the manufacture of your OTC hand sanitizer drug products. Additionally, there were deficiencies in your production documentation including, but were not limited to:
- Material lot numbers were not always recorded.
- Quantities used in the batch were recorded as ranges in some cases.
- No equipment identification numbers were recorded.
- No mixing speeds/times were recorded.
- There is a lack of operator and verifier initials for weighing and material addition steps.
- There were no packaging instructions or representative labels collected.
In response to this letter, provide:
- A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
Superior Glove Works, Ltd., Acton FEI 3006217765 page 5
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.
Note that FDA placed all drugs and drug products manufactured by your firm on Import Alert 66-40 on September 27, 2022, 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.
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 3006217765 and ATTN: Frank Wackes.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
Hubert Parsons - email@example.com
1 Due to an increased demand for alcohol-based hand sanitizers during the COVID-19 pandemic, FDA published the Guidance for Industry: Temporary Policy for Preparation of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency (COVID-19) on March 19, 2020, and subsequently updated the guidance several times. The guidance was withdrawn effective December 31, 2021 (86 Fed Reg at 56960). 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 are present. These circumstances included preparation of hand sanitizer products using only the ingredients and formulas set forth in the guidance. Because Superior Glove Works, Ltd. hand sanitizer drug products were not consistent with the formulations described in these guidances, they did 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.