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Warning Letter 630110

September 1, 2022

Dear Mr. Stefansky and Mr. Iskowitz:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Shuzy Rock Inc, FEI 3013835844, at 161 Helen Street, South Plainfield, from January 11 to February 14, 2022.

FDA determined that drug products manufactured at your facility, including “Premium Nature INSTANT HAND SANITIZER”, are adulterated within the meaning of section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic (the FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions.

The results of the FDA laboratory testing of batches of these products distributed in the U.S. market also demonstrate that these drug products represented to be manufactured at your facility are adulterated within the meaning of section 501(c) of the FD&C Act, 21 U.S.C. 351(c), in that its strength, purity, or quality falls below that which it purports or is represented to possess.

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 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).

Additionally, Shuzy Rock Inc is not duly registered with FDA as required by section 510 of the FD&C Act and 21 CFR Part 207. With some limited exceptions, firms that manufacture, prepare, propagate, compound, or process drugs in the United States, or that are offered for import into the United States, must be registered with the FDA (Sections 510(b), (c), (d), and (i) of the FD&C Act, 21 U.S.C. 360(b), (c), (d), and (i)).

Premium Nature INSTANT HAND SANITIZER, Premium Nature INSTANT HAND SANITIZER TRAVEL SIZE, (b)(4) INSTANT HAND SANITIZER GEL, (b)(4) SHAMPOO, and (b)(4) CONDITIONER FOR MEN AND WOMEN are not duly listed with FDA as required by section 510(j) of the FD&C Act. Failure to properly list a drug product is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). Introduction or delivery for introduction of such products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.

Insanitary Conditions

Your drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, or held under insanitary conditions. FDA investigators observed your facility to be in a state of disrepair, poorly cleaned and maintained as evidenced by refuse on the floors, unaddressed spills, and broken tiles along the base of the wall in the filling room. You do not have adequate controls in place to maintain a clean production environment and prevent cross-contamination of drug products and non-drug products manufactured at your facility.

Additionally, you manufactured drug products using nondedicated equipment without adequate, validated cleaning procedures. Your equipment, including filling machines, were found to be soiled during the FDA inspection. FDA analysis of your marketed hand sanitizer drug product found impurities including polymers, silicate type material, and rust-colored particles which may have originated from product cross-contamination on nondedicated equipment and poorly maintained equipment.

FDA Tested Samples

Adulteration Violations: Subpotency

Premium Nature INSTANT HAND SANITIZER, represented to be manufactured at your facility, is labeled to contain 65% volume/volume (v/v) of the active ingredient alcohol (ethanol). However, FDA laboratory testing of batches of this product distributed in the U.S. market found that the drug product contained a range of 48 – 57% v/v ethanol.

Additionally, Premium Nature INSTANT HAND SANITIZER, manufactured at your facility, is labeled to contain 70% v/v of the active ingredient alcohol (ethanol). However, FDA laboratory testing of a batch of this product distributed in the U.S. market found that the drug product contained 55% v/v ethanol. Therefore, these hand sanitizer drug products are adulterated under section 501(c) of the FD&C Act in that the active ingredient of ethanol is present at levels in the products lower than what is declared on their labeling.

CDC recommends¹ that, if soap and water are not readily available, consumers should use an alcohol-based hand sanitizer that contains not less than 60% alcohol (ethanol). This is the minimum active ingredient concentration of ethanol specified in the 1994 Tentative Final Monograph for Health-Care Antiseptic Drug Products (59 FR 31402), as further amended by “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016).

On January 7, 2022, FDA held a teleconference with your contract manufacturer, (b)(4). We recommended that they consider removing all of the firm’s Premium Nature hand sanitizer drug product(s) currently in distribution from the U.S. market and within expiry.

On January 20, 2022, FDA held a teleconference with you and your counsel. We recommended that you consider removing all of your firm’s hand sanitizer drug products currently in distribution from the U.S. market and within expiry.

On January 24, 2022, FDA notified the public of the subpotency of your hand sanitizer drugs 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:

• A detailed investigation into how the hand sanitizer drug product described above, labeled as containing 65% (v/v) ethanol, in fact contained an average of 48 – 57% ethanol and how hand sanitizer product described above, labeled as containing 70% (v/v) ethanol, in fact contained an average of 55% ethanol.
• 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 distributed in the U.S., and a full reconciliation of all material you distributed.
• Copies of the complete batch records for all batches distributed in the United States.

The subpotency of hand sanitizer drug products represented to be manufactured in your facility 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.²

CGMP Violations

We reviewed your March 7, 2022, response to our Form FDA 483 in detail. 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’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 for oversight for the manufacture of your over-the-counter (OTC) drug products. You could not identify any personnel with the responsibility and authority of the Quality Unit (QU). You could not provide procedures for investigations, recalls, complaint handling, the approval of manufacturing instructions, and the evaluation and approval or rejection of finished drug product batches before release to the market. Likewise, your firm did not have a procedure for the evaluation and approval or rejection of incoming materials. As such, your firm utilized (b)(4) that was not USP grade for the manufacture of your hand sanitizer drug products.

The CGMP regulations assign responsibilities to the 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 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.

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 batch 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 corrective action and preventive action plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.

2. 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)).

Inadequate Process Controls

Your production instructions and production records were inadequate to ensure consistent manufacture of OTC drug products. Your hand sanitizer manufacturing “recipe” lacked critical parameters such as equipment identification, mixing speeds, component addition rates, filling parameters, and bottle fill volume. Likewise, you failed to provide executed batch records, or any other information recorded during the manufacture of distributed hand sanitizer batches.

Inadequate Cleaning Controls

Your cleaning procedures were inadequate. For example, your “Clean Production Area” procedure prescribed a “deep clean” of the production room (b)(4) but did not describe this process with sufficient detail. Additionally, you failed to have cleaning instructions for specific manufacturing equipment. Your cleaning schedule was not supported by validation studies and you did not maintain cleaning records. Lastly, your production area was not observed to be in a clean state and your filling equipment was soiled.

Inadequate Water System Design and Controls

Your water system which is used to generate water used in the manufacture of your drug products is inadequately designed and controlled for its intended use. Your firm uses (b)(4) water without additional treatment, monitoring, or testing. Water is carried through your facility (b)(4) that was observed to be in the same position on January 24, 2022, and January 25, 2022, during the FDA inspection. It did not appear that the (b)(4) was dismantled for cleaning and you failed to provide cleaning procedures or records. The positioning of the (b)(4) within which water could pool and support microbial growth. Your water system design, monitoring plan, and cleaning procedures are inadequate for OTC drug manufacturing.

In response to this letter, provide:

• A remediation plan that better assures ongoing management oversight throughout the manufacturing lifecycle of all drug products. Provide a more data-driven and scientifically sound program that identifies sources of process variability, and assures that manufacturing including both production and packaging operations meet appropriate parameters and quality standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step and its controls, and vigilant ongoing monitoring of process performance and product quality.
• An assessment of each drug product process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes, and will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.
• Timelines for completed process performance qualification for marketed drug products.
• A comprehensive, independent assessment of your water system design, control, and maintenance.
• A thorough remediation plan to install and operate a suitable water system. Include a robust ongoing control, maintenance, and monitoring program to ensure the new system consistently produces water adhering to Purified Water, USP monograph specifications and appropriate microbial limits. Regarding the latter, ensure that your total microbial count limit for water is appropriate in view of the intended use of the products produced by your firm.

3. 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 perform adequate drug product testing prior to release to the market. You could not provide a list of tests, specifications, or test procedures used as part of batch release. Likewise, you could not provide release testing results for distributed batches. As noted above, FDA testing found your hand sanitizer products to be subpotent and contaminated with other impurities.

In response to this letter, provide:

• A list of chemical and microbiological specifications, including test methods, used to analyze each lot of your drug products before a lot of disposition decision.

  o 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 U.S. that are within expiry as of the date of this letter.
  o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.

Establishment Registration and Drug Listing Violations

Shuzy Rock Inc manufactures drug products as detailed in an FDA inspection conducted on January 11, 2022. Under section 510(b) of the FD&C Act, 21 U.S.C. 360(b), and 21 CFR 207.17(a), all manufacturers must register each establishment. Additionally, firms must review and update registration information annually or certify that there are no changes in accordance with 21 CFR 207.29. Our query of FDA’s drug registration and listing database showed that Shuzy Rock Inc (FEI: 3013835844) was never registered with FDA. Shuzy Rock Inc is required to submit registration information annually by electronic means for each establishment it owns or operates that is engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is in commercial distribution in the United States. Shuzy Rock Inc has not fulfilled its registration requirement. Failure to register in accordance with section 510 of the FD&C Act or to provide any information required by section 510(j) is a prohibited act under section 301(p) of the FD&C Act, 21 U.S.C. 331(p). In addition, all drugs manufactured in such establishment not duly registered under section 510 are misbranded under Section 502(o) of the FD&C Act, 21 U.S.C. 352(o).

Under section 510(j)(1) of the FD&C Act, 21 U.S.C. 360(j)(1), and 21 CFR 207.41, all drugs manufactured, prepared, propagated, compounded, or processed for U.S. commercial distribution must be listed with FDA. Premium Nature INSTANT HAND SANITIZER, Premium Nature INSTANT HAND SANITIZER TRAVEL SIZE, (b)(4) INSTANT HAND SANITIZER GEL, (b)(4) SHAMPOO, and (b)(4) CONDITIONER FOR MEN AND WOMEN have never been listed with FDA. Failure to properly list a drug product is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o).

The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).

Drug Production Ceased

We acknowledge your written notification that you have ceased manufacturing hand sanitizers as of September 2020, and have no intention of resuming production of hand sanitizers drug products or any other drug product in the future.

If you plan to resume any manufacturing regulated under the FD&C Act, notify this office prior to resuming your drug manufacturing operations. If you resume CGMP activities, you are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In addition, 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 evaluate the completion and efficacy of all corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.

Center for Food Safety and Applied Nutrition Concerns

In addition, we note that some of the products you repack are regulated as cosmetics, as defined in section 201(i) of the Federal Food, Drug and Cosmetic Act (the Act). A cosmetic is adulterated under section 601(c) of the Act [21 U.S.C. 361(c)] if it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health. The conditions at your facility, which are described elsewhere in this letter, may cause the cosmetic products you repack to be adulterated. We note that under section 301(a) of the Act [21 U.S.C. 331 (a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic product that is adulterated.

Conclusion

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 FDA to withhold issuance of Export Certificates. 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.

Send your electronic response to orapharm1_responses@fda.hhs.gov. Your written notification should refer to Warning Letter CMS # 630110 and include FEI: 3013835844.

If you have any questions, contact Compliance Officer Barbara Wilimczyk-Macri at barbara.wilimczyk@fda.hhs.gov .

Sincerely,
/S/

Nerizza Guerin
Acting Program Division Director
Office of Pharmaceutical Quality Operations Division I

_____________________

1 https://www.cdc.gov/handwashing/hand-sanitizer-use.html

2 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 public health emergency (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.