FDA 483 Warning Letter Dated JUNE 22, 2022
1. 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)) and the company failed to prove this procedure.
The company manufactured an OTC drug product, MOISTURIZING HAND SANITIZER Peppermint Scented. Company 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, Company provided records that 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 the Company response, 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, is used to analyze each batch of your drug products before a batch disposition decision. Specify which tests are performed by your facility and which, are performed by a contract testing laboratory (if any,).
- An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug products 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. To conduct at least one test to verify the identity of each component of a drug product. Your company 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)) and the company failed to prove this procedure.
Based on the records and information provided by the Company, 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 the information provided by suppliers.
For example, in response to our request for information pertaining to identity testing of raw materials, the company 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 the Company response, 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 the use of unsuitable components, containers, and closures.
3. 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)) and the company failed to prove this procedure.
Based on the records and information the company provided, the company did not demonstrate that firm established and followed an adequate stability program to determine appropriate storage conditions and expiration dates of drug products manufactured at your facility.
The company has failed to provide the expiry dates of hand sanitizer drug products manufactured at your facility in response to our specific request. Additionally, the firm 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 the Company response, provide the following:
• A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. the firm 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.
Misbranding Violation
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)) and section 201(g)(1)(C) of the FD&C Act (21 U.S.C. 321(g)(1)(C))
- Because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
- 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 of the product (as defined in 21 CFR 201.128) 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 SANITIZERS, including the product, that provides evidence of the intended uses 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.
The qualified consultant performs
A comprehensive audit of your entire operation for CGMP compliance,
Evaluates the completion and efficacy of your corrective actions and preventive actions before you pursue the resolution of your firm’s compliance status with the FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP.
