Gordon Laboratories Inc.

Your facility is registered with the U.S. Food and Drug Administration as a manufacturer of over-the-counter (OTC) drug products, including consumer antiseptic hand rub drug products (also referred to as consumer hand sanitizers). The FDA conducted testing of a consumer hand sanitizer drug product, labeled as artnaturals SCENT FREE HAND SANITIZER. This drug product was manufactured at your drug manufacturing facility, Gordon Laboratories Inc., FEI 2012546, at 751 E Artesia Blvd., Carson, California, and distributed in the United States.

The results of the FDA laboratory testing of batches of artnaturals SCENT FREE HAND SANITIZER 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 (FD&C Act), 21 U.S.C. 351(a)(2)(B)1.

Additionally, the FDA inspected your drug manufacturing facility, Gordon Laboratories, Inc., FEI 2012546, at 751 E Artesia Blvd., Carson, California, from February 8 to March 10, 2022. This inspection followed the violative sample results of the consumer hand sanitizer, labeled as artnaturals SCENT FREE HAND SANITIZER.

This warning letter 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).

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding 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).

Your firm is a contract manufacturer of artnaturals SCENT FREE HAND SANITIZER.

FDA laboratory testing of a batch of artnaturals SCENT FREE HAND SANITIZER in U.S. distribution was found to contain impurities at unacceptable levels1. Benzene impurity levels were found to be approximately 15 parts per million (ppm), while acetaldehyde and acetal impurities were found to be approximately 146 ppm and 469 ppm, respectively.

Acetaldehyde appears to be genotoxic, and potentially carcinogenic, when in direct contact with tissues. The 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 October 4, 2021, the FDA notified the public of the unacceptable impurity results for artnaturals SCENT FREE HAND SANITIZER at the following website: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use

On October 8, 2021, the FDA held a teleconference with you, and your customer, Virgin Scent Inc. (dba Artnaturals), to whom your firm acts as a contract manufacturer for artnaturals SCENT FREE HAND SANITIZER, and we recommended to consider removing the adulterated batch of artnaturals SCENT FREE HAND SANITIZER drug product currently in distribution from the U.S. market. On October 26, 2021, you, and Virgin Scent Inc., issued a voluntary nationwide recall of two batches of artnaturals SCENT FREE HAND SANITIZER due to the presence of benzene, acetaldehyde, and acetal impurities. On April 22, 2022, the scope of the recall of artnaturals SCENT FREE HAND SANITIZER was expanded to include at least 38 additional batches because they were manufactured using some of the same ingredients as the two batches initially recalled. Refer to the following FDA website: https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/artnaturalsr-issues-voluntary-recall-limited-batches-8oz-bottles-scent-free-hand-sanitizer-due

The contamination with benzene, acetaldehyde, and acetal impurities in a drug product manufactured in your facility, in addition to the significant violations documented in the inspection, 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 Act1.

We reviewed your March 31, 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 thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

Hand Sanitizer Drug Product

You failed to adequately investigate the root cause of the benzene, acetal, and acetaldehyde impurities found in the artnaturals SCENT FREE HAND SANITIZER drug product.

During the inspection, the investigators found that there was a lack of investigation into the failure of the batches that were voluntarily recalled. Furthermore, you failed to identify whether other batches were impacted or initiate testing of the retain samples of other batches that are in U.S. distribution.

In your response, you identify that the “more probable root cause for the introduction of Benzene was from the (b)(4)” and that “this was due to the fact that not all grades and all manufacturing processes of (b)(4) result in the same purity.” However, your response does not provide evidence from the out-of-specification (OOS) investigation or formal risk assessment process which led to this conclusion, nor does the response address the root cause for the unacceptable levels of the acetal and acetaldehyde impurities.

Furthermore, drug products must be tested for identity, strength, quality, and purity prior to release and distribution. Manufacturers are required to establish and validate or verify analytical methods and procedures to ensure the accuracy, sensitivity, specificity, and reproducibility of testing. Considering the known risk of benzene contamination, including the FDA test results demonstrating benzene, a finished product specification for benzene in your hand sanitizers is appropriate under 21 CFR 211.160(b).

As of the date of this letter, you have yet to provide complete impurity results of the other batches in U.S. distribution. We acknowledge that you expanded the voluntary recall to include additional batches of hand sanitizer manufactured with common components used in the recalled batches. However, we remain concerned about the quality of the individual components and the remaining batches of hand sanitizer drug product still in U.S. distribution which lack adequate testing.

Water System

You lacked investigations into multiple microbiological monitoring results from your water system that exceed action limits. For example, you did not investigate multiple results above your total aerobic microbial count action limit of (b)(4) cfu/g. Furthermore, during the inspection, data to support the quality of the water system before July 2021, was not available nor provided.

You acknowledged these deficiencies in your response, but failed to include a risk assessment or retrospective review to determine whether the out-of-limit results and/or the lack of water testing results have impacted released drug product; nor did you discuss the impact of the failure to follow your established procedures regarding microbiological events.

Inadequate investigations can lead to unidentified root causes, ineffective corrective action and preventive action (CAPA), and recurring problems that compromise the ability to produce safe and effective drug products.

In response to this letter, provide:

A comprehensive independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.

Summary of all available water system results from all parties (whether third party laboratory or in-house testing) including the identification of organism for any results (whether from potable water or points of use ports) above the alert and action levels or for any organism presence detected during the selected indicator organism test.

A summary of all results including methanol, benzene, acetal, and acetaldehyde for all hand sanitizer batches released and distributed. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

Your firm failed to test incoming components prior to their use in the manufacture of artnaturals SCENT FREE HAND SANITIZER. You also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals, or used incoming components without COAs. For example, one lot of carbomer material was received from an unapproved supplier and a second lot was received without a COA from an unknown supplier. These components were used in the manufacture of hand sanitizer drug products; specifically in two hand sanitizer batches which were subsequently recalled because of the presence of impurities.

In your response, you stated that your process to manage shipments under quarantine is under revision and that all hand sanitizer batches that were shipped under quarantine had “(b)(4).” However, your response does not explain whether product had been distributed (b)(4) nor was an adequate investigation and retrospective review performed to determine whether other components were received from unapproved suppliers and/or with incomplete testing of the incoming component prior to their use in production of drug products. Additionally, your response does not address how you will prevent the use of poor-quality components in future batches.

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 drug products.

In your response to this letter, provide:

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.

Investigation and risk assessment regarding all instances for all drug products where material was received without COA, or where the material may not have been sampled, tested, or released by the quality unit prior to use in production.

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, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

You use water as a component in the manufacture of your drug products. You failed to ensure the water system is designed, maintained, and monitored in a validated state. For example, validation of your water system has not been performed and you were unable to provide microbiological monitoring of water system before July 2021.

Your response states that you expect to complete validation (after the systematic review) by the (b)(4). However, your response is inadequate because you have not provided sufficient details how you will ensure that your current water system design is appropriate for its intended use while the system is being remediated. Furthermore, your sampling frequency and your microbial testing is inadequate since water system samples are not currently monitored for the presence of Burkholderia Cepacia Complex (BCC).

The lack of data regarding the state of control of your water system poses a potential risk objectionable microbiological contamination into your drug products. Pharmaceutical water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.

In your response to this letter, provide:

A comprehensive remediation plan for the design, control, and maintenance of the water system including robust monitoring program to ensure the remediated system design consistently produces water adhering to (b)(4), United States Pharmacopeia (USP) monograph specifications and appropriate microbial limits.

Validation report for the water system obtained after all identified design issues have been fully corrected and any maintenance repairs have been completed. Include the system validation protocol, the complete test results, and the final validation report.

Your total microbial count limits to monitor whether this system is producing water suitable for the intended uses for each of your products.

A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug products currently in U.S. distribution. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.

For further information regarding the significance of Burkholderia Cepacia Complex and other objectionable contamination of non-sterile, water-based drug products, see FDA’s advisory notice posted on July 7, 2021, at https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-drug-manufacturers-burkholderia-cepacia-complex-poses-contamination-risk-non-sterile

Your firm’s quality systems are inadequate. 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.

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. The qualified consultant should also perform a comprehensive audit of your entire operation for CGMP compliance and the consultant should also evaluate the completion and efficacy of any identified corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with the FDA.

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 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.

Please send your electronic reply to ORAPHARM4_Responses@FDA.HHS.GOV or mail your reply to:

CDR Steven E. Porter, Jr. Director, Division of Pharmaceutical Quality Operations IV U.S. Food & Drug Administration 19701 Fairchild Road Irvine, California 92612-2506

Please identify your responses with the unique identifier: CMS 631432

If you have questions regarding the contents of this letter, please contact Andrew Haack, Compliance Officer by telephone at 206-340-8212 or email at Andrew.Haack@fda.hhs.gov.