- Delivery Method:
- VIA UPS
Recipient NameMr. Arun Pasricha
- Clean Cosmetics LLC
621 Fitch Avenue
Moorpark, CA 93021-2061
- Issuing Office:
- Division of Pharmaceutical Quality Operations IV
January 30, 2023
Dear Mr. Pasricha:
The U.S. Food and Drug Administration inspected your drug manufacturing facility, Clean Cosmetics LLC, FEI 3015237167, at 621 Fitch Avenue, Moorpark, CA, from August 11 to 19, 2022. This inspection followed our January 26, 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, of which the FDA has reviewed the records you submitted in response.
This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug product is adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).
We reviewed your September 9, 2022, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence. Your response is inadequate because it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.
During our inspection, our investigators observed specific violations 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. 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)).
You failed to adequately test your incoming components for identity before using the components to manufacture your over-the-counter (OTC) drug products. Your firm accepts test results from supplier certificates of analysis (COA) without performing identification testing. Additionally, you could not provide evidence that you had evaluated your suppliers’ quality oversight, manufacturing operations, or verified results listed on the COAs they provided to you. Your firm received components for the manufacture of hand sanitizer1 as well as bulk hand sanitizer for repackaging and relabeling.
Additionally, your review of supplier COAs was inadequate. You provided a supplier COA showing that the ethanol lot received and used for drug product manufacture contained (b)(4) volume/volume methanol. While you indicated that the hand sanitizer drug product manufactured with this lot of ethanol was not distributed to the market, your firm manufactured and released (b)(4) lots of hand sanitizer drug product using ethanol, which contained unacceptable levels of methanol. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See the FDA’s guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19) to help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/media/145262/download.
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.
- 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 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 that describes this COA validation program.
- A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.
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)).
Your firm failed to establish adequate laboratory controls and specifications for your TrustRX Medical Grade Hand Sanitizer drug product. Specifically, you failed to perform microbial testing and impurity testing on your finished hand sanitizer drug products. Without testing each lot prior to release, you did not have scientific evidence that all drug product lots conformed to the appropriate quality specifications.
In response to this letter, provide:
- A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.
- An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all lots 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 retain samples from each lot. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.
3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).
Your firm failed to have adequate procedures and personnel with the CGMP responsibilities and authority for oversight of the manufacture of your OTC drug products. You could not provide procedures for investigations, corrective actions and preventive actions (CAPAs), change controls, recalls, qualification of suppliers, equipment cleaning, and water system monitoring. Likewise, your firm releases components for use in manufacturing without identity testing and releases completed lots without appropriate release testing.
Your response states that your firm is in the process of developing and implementing a fully compliant quality system and is working with a consultant. No further details, timeline, or action plan were provided.
The CGMP regulations assign responsibilities to the quality unit (QU) which include approving or rejecting incoming materials, in-process materials, and drug products; ensuring that controls are implemented and completed satisfactorily during manufacturing operations; and reviewing production records and investigating any unexplained discrepancies. You have not demonstrated that you have a QU capable of these responsibilities.
See the 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:
In response to this letter, provide:
- 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 lot 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 complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
Public Notification About Your Hand Sanitizer Product
On January 26, 2022, the FDA sent you a request for records and other information pursuant to section 704(a)(4) of the FD&C Act related to your hand sanitizer manufacturing operations. You provided a COA for ethanol lot (b)(4) which contained (b)(4) methanol. In a follow-up communication on May 17, 2022, the FDA requested your distribution records for any hand sanitizer drug product manufactured with this lot of ethanol. Your firm failed to respond. The FDA made additional attempts between July 21 to 27, 2022, to set up a teleconference with your firm or with your consultant regarding this product and you failed to respond.
On August 3, 2022, the FDA notified the public of the methanol content in your TrustRX Medical Grade Hand Sanitizer drug product at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use
Destruction of Adulterated Product
Following the inspection, you committed in your September 9, 2022 response and October 28, 2022 response update, to destroy all TrustRX Medical Grade Hand Sanitizer drug product containing an unacceptable level of methanol. We observed removal of these products from your facility on November 10, 2022 by a disposal company.
CGMP Consultant Recommended
Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. 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.
Drug Production Ceased
We acknowledge your commitment to cease production of drugs at this facility. In response to this letter, clarify whether you intend to resume manufacturing any drugs at this facility in the future. If you plan to resume manufacturing drugs, ensure that adequate corrective actions are in place and notify this office to schedule a meeting before resuming your operations.
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.
Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure, and injunction. Unresolved violations may also prevent other federal agencies from awarding contracts.
Failure to address violations may also cause the FDA to withhold issuance of export certificates. The 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 re-inspect to verify that you have completed corrective actions to address any violations.
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 days2. 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.
Please identify your response with unique identifier CMS 643205. Electronic responses may be submitted to ORAPHARM4_Responses@fda.hhs.gov with ATTN: CDR Steven E. Porter, Jr. or send your written responses to:
CDR Steven E. Porter, Jr. Director,
Division of Pharmaceutical Quality Operations IV
U.S. Food and Drug Administration
1907 Fairchild Road
Irvine, CA 92612
If you have questions regarding this letter, please contact LCDR Rumany Penn, compliance officer, at (949) 608-4409, or by email at Rumany.Penn@fda.hhs.gov.
CDR Steven E. Porter, Jr.
Director, Division of Pharmaceutical Quality Operations IV
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 Clean Cosmetics LLC hand sanitizer drug products were not prepared under the circumstances described in this guidance, they did 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 Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from the FDA on the adequacy and completeness of your corrective action plans.