- Delivery Method:
- VIA UPS
Recipient NameMr. Moon Su Eun
- Mirfeel Korea Co., Ltd.
77 Hwanggeum-ro 323 beon-gil
- Issuing Office:
- Center for Drug Evaluation and Research | CDER
Warning Letter 320-22-16
June 22, 2022
Dear Mr. Eun:
Your facility is registered with the U.S. Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products, including consumer antiseptic hand rub drug products (also referred to as consumer hand sanitizers). FDA conducted testing of a consumer hand sanitizer drug product, labeled as MOISTURIZING HAND SANITIZER Peppermint Scented. This drug product was manufactured at your facility, Mirfeel Korea Co., Ltd., FEI 3016921925, 77 Hwanggeum-ro 323 beon-gil, Yangchon-eup, Gimpo, Gyeonggi- do, Republic of Korea, and distributed in the U.S.
The results of the FDA laboratory testing of a batch of this product in U.S. distribution demonstrate that this drug product manufactured at your facility is adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 351(a)(2)(B))1, in that contamination with the impurity benzene at unacceptable levels demonstrates that the quality assurance within your facility is not functioning in accordance with Current Good Manufacturing Practice (CGMP) requirements.
Additionally, FDA has reviewed the records you submitted in response to our initial August 3, 2021 request for records and other information, and subsequent correspondence, pursuant to section 704(a)(4) of the FD&C Act for your facility. 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)).
This warning letter also summarizes significant violations of CGMP regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
In addition, your MOISTURIZING HAND SANITIZER product line packaged in 1.01 ounce containers2 that resemble food pouches customarily purchased by U.S. consumers are misbranded under section 502(i) of the FD&C Act (21 U.S.C. 352(i)). In this letter, we collectively refer to these products as “MOISTURIZING HAND SANITIZERS.” 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.
MOISTURIZING HAND SANITIZER Peppermint Scented was manufactured at your facility. FDA laboratory testing of a batch of this product in U.S. distribution found that the drug product contained impurities at unacceptable levels. Benzene impurity levels were found to be between 5 parts per million (ppm) to 6 ppm.
Manufacturers should not use benzene in the manufacture of drugs because it is a known human carcinogen that causes leukemia and other blood disorders. FDA has alerted all drug manufacturers to the known risk factors for contamination with benzene. For more information see https://www.fda.gov/drugs/pharmaceutical-quality-resources/fda-alerts-drug-manufacturers-risk-benzene-contamination-certain-drugs
On February 10, 2022, FDA held a teleconference with you. We recommended you consider removing the adulterated batch of MOISTURIZING HAND SANITIZER Peppermint Scented drug product currently in distribution from the U.S. market. We also requested that you commit to providing impurity testing results, including for benzene, for all batches of hand sanitizer drug product sent to the U.S. market which are within expiry. Because benzene contamination is a known risk of the manufacturing process, a finished product specification for benzene in hand sanitizers is appropriate under 21 CFR 211.160(b). Further, finished product testing of each batch of drug product and documentation thereof are required by 21 CFR 211.165. As of the date of this letter, you have yet to initiate a recall or provide complete impurity testing results.
On February 23, 2022, FDA notified the public of the unacceptable benzene results in your hand sanitizer drug products at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
In response to this letter, provide the following:
- A detailed investigation into how the hand sanitizer drug product described above, which was manufactured at your facility, contained unacceptable levels of benzene contamination.
- A list of all raw materials used to manufacture 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 U.S. 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.
- Impurity testing results (including benzene impurity testing results) for all batches of hand sanitizer drug products sent to the U.S. market which are within expiry.
The contamination with benzene in a drug product manufactured in your facility, in addition to the deficiencies in your response to the information we requested during the February 10, 2022 teleconference, 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 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 firm manufactured an OTC drug product, MOISTURIZING HAND SANITIZER Peppermint Scented. Your response to our request for records and other information under section 704(a)(4) indicated that you did not conduct adequate finished drug product testing on all drug products shipped to the U.S.
Specifically, you provided records which demonstrate that your hand sanitizer drug product is only tested for appearance, odor, pH, viscosity, and specific gravity. Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product 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 the following:
- Methanol, benzene, acetal, and acetaldehyde test results for all hand sanitizer batches released and distributed.
- A list of chemical and microbiological specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision. Specify which tests are performed by your facility and which, if any, are performed by a contract testing laboratory.
- 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.
- 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.
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 211.84(d)(2)).
Based on the records and information you provided, you did not demonstrate that you are adequately testing each lot of incoming raw materials used to manufacture your drug products to determine their identity, and you accepted test results from suppliers without verifying information provided by suppliers.
For example, in response to our request for information pertaining to identity testing of raw materials, you only submitted the component’s Certificate of Analysis (COA). You did not provide specific identity testing records, and there is no indication that you have established the reliability of your component supplier’s analyses through adequate initial validation and subsequent verification of the supplier’s test results at appropriate intervals.
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 components 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 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 did not demonstrate that you established and followed an adequate stability program to determine appropriate storage conditions and expiration dates of drug products manufactured at your facility.
You have failed to provide the expiry dates of hand sanitizer drug products manufactured at your facility in response to our specific request. Additionally, you reported that stability tests were only composed of appearance and physical characteristic testing. Without appropriate stability studies, there is no scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.
In response to this letter, provide the following:
• A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:
o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.
o Stability-indicating methods.
o An ongoing program in which representative batches of each drug product are added each year to the program to determine if the shelf-life claim remains valid.
o Detailed definition of the specific attributes to be tested at each station (timepoint).
• All procedures that describe these and other elements of your remediated stability program.
MOISTURIZING HAND SANITIZERS 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 topical consumer antiseptics.
Examples of claims observed on the product label for MOISTURIZING HAND SANITIZER Peppermint Scented that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the product include, but may not be limited to, the following:
“Hand Sanitizer . . . Anti-Bacterial”
“Drug Facts . . . Purpose Antiseptic . . . Uses ◦ to decrease bacteria on the skin that could cause disease . . . Directions ◦ wet hands thoroughly with product and allow to dry without wiping . . . .”
Examples of claims observed on the product labeling for MOISTURIZING HAND SANITERS, including the product website https://www.thecremeshop.com/, that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products include, but may not be limited to, the following:
“Hand Sanitizer . . . Anti-Bacterial”
“How To Use 1. Wet hands thoroughly with product and allow to dry without wiping.”
Section 502(i)(1) of the FD&C Act (21 U.S.C. 352(i)(1)) provides that a drug is misbranded if “its container is so made, formed, or filled as to be misleading . . .” On August 27, 2020, FDA published a news release titled, “COVID-19 Update: FDA Warns Consumers About Hand Sanitizer Packaged in Food and Drink Containers,” see https://www.fda.gov/news-events/press-announcements/covid-19-update-fda-warns-consumers-about-hand-sanitizer-packaged-food-and-drink-containers. This news release warns consumers about alcohol-based hand sanitizers packaged in containers that resemble food or drink containers customarily purchased by U.S. consumers and may put consumers at risk of serious injury or death if ingested.
Your MOISTURIZING HAND SANITIZERS are packaged in containers that resemble food pouches customarily purchased by U.S. consumers. OTC hand sanitizer drug products packaged in containers that resemble food pouches commonly used by adults and children may mislead consumers into believing the products are food and, thereby, increase the risk of accidental ingestion. As such, your OTC hand sanitizers, packaged in 1.01 ounce containers that have a similar shape, size, and function as a pouch ordinarily used to package food are misbranded under section 502(i)(1) of the FD&C Act (21 U.S.C. 352(i)(1)).
The introduction or delivery for introduction of misbranded drugs 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.
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 Alerts 66-78 and 66-40 on March 24, 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 these import alerts 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.
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 CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3016921925.
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research, FDA
Registered U.S. Agent:
J.S. Chem International Co.
3530 Wilshire Blvd. Suite 1210
Los Angeles, CA 90010-2318
1 We note that your drug product also does not conform to any temporary policy FDA has implemented during the public health emergency (PHE). In March 2020, the Agency published three guidance documents to provide regulatory flexibility to certain firms to help meet the demand for alcohol-based hand sanitizer during the COVID-19 PHE. Additionally, on December 31, 2021, these guidances were withdrawn, and firms were required to cease distribution, by March 31, 2022, of any remaining hand sanitizer products that were prepared under the temporary policies before or on December 31, 2021. See, 86 FR 56960, October 13, 2021.
2 This includes the products MOISTURIZING HAND SANITIZER Eucalyptus Scented, MOISTURIZING HAND SANITIZER Green Tea Scented, MOISTURIZING HAND SANITIZER Strawberry Scented, MOISTURIZING HAND SANITIZER Candy Apple Scented, MOISTURIZING HAND SANITIZER Watermelon Scented, MOISTURIZING HAND SANITIZER Mixed Berries Scented, MOISTURIZING HAND SANITIZER Peach Scented, MOISTURIZING HAND SANITIZER Peppermint Scented, and (b)(4) that are packaged in 1.01 oz. containers.