Nature’s Fusions LLC

The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Nature’s Fusions LLC, FEI 3012853845, at 57 North 1380 West, Orem, Utah, from January 15 to 21, 2025.

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 Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

We have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.

During our inspection, our investigator observed specific violations including, but not limited to, the following.

1. Your firm failed to establish a written testing program designed to assess the stability characteristics of drug products and determine appropriate storage conditions and expiration dates. Your firm also failed to have buildings used in the manufacture, processing, packing, or holding of drug products with adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination (21 CFR 211.166(a) and 21 CFR 211.42(b)).

Your facility repackages and manufactures over-the-counter (OTC) drug products, such as hand sanitizers. You failed to establish an adequate stability program that includes adequate chemical and microbial testing and lacked adequate controls for material storage.

Lack of Stability Studies

You used expired bulk ethanol hand sanitizer gel for repackaging into smaller units and assigned a two-year expiry date without conducting stability studies. In addition, you did not conduct stability studies for isopropyl alcohol (IPA) spray hand sanitizers manufactured onsite to demonstrate that your OTC drug products will remain acceptable throughout their assigned two-year expiry period.

Inadequate Material Storage

Bulk totes of ethanol hand sanitizer gel were stored outdoors, and you informed our investigator that these totes had been stored outdoors since April 2020. Labeling for the bulk ethanol hand sanitizer gel lists a temperature storage range of (b)(4) F. The totes are exposed to temperature excursions that often exceed the specified temperature storage range, which could compromise the quality of the drug product therein.

In response to this letter, provide:

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 indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each 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).o All procedures that describe the listed elements of your remediated stability program.

A comprehensive, independent assessment of all drug products in the U.S. market to determine if you have data to support that they conform to specifications throughout their shelf-life, including evaluating storage conditions, differences in each formulation, packaging configurations, and all historical stability studies that have been performed. If there are gaps in the data needed to scientifically support that your drug products retain their quality attributes through their labeled shelf-life, provide a CAPA plan which will include an impact assessment for any batches that remain within their shelf-life in the market.

A summary of results from testing reserve samples within expiry for all drug product batches not currently in your existing stability program. Testing of each batch should be completed within 60 days of this letter. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients as well as microbiological quality of each batch. If testing yields an out-of-specification result, indicate the corrective actions you will take, including notifying customers and initiating recalls.

2. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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 test all incoming raw materials, including isopropyl alcohol received from suppliers, used to manufacture your OTC hand sanitizer drug product. You relied on your supplier’s certificate of analysis (COA) for components, such as isopropyl alcohol, in lieu of testing each component for purity, strength, identity, and quality.

You manufacture drugs that contain IPA. Methanol substitution in alcohols has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol at https://www.fda.gov/media/173005/download.

Without adequate testing and confirmation of reliability of supplier and external laboratory testing results, you lack scientific evidence that the components or drug products conform to appropriate specifications.

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 summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedures that describes this COA validation program.

A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.

Methanol testing for all hand sanitizer batches released and distributed in the United States within expiry.

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. Your firm also failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)).

You failed to conduct adequate finished product release testing for each batch of your drug product, including but not limited to, testing the identity and strength of the active ingredient, isopropyl alcohol and testing for objectionable microorganisms. For example, your COA for (b)(4) indicates that you calculated the assay value instead of performing testing, and that you only performed organoleptic evaluation for appearance, color, and odor.

Drug product batches must be tested for identity, strength, and purity prior to release. Testing is an essential part of ensuring that the drug products you manufacture conform to all predetermined quality attributes and are appropriate for their intended use. Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release.

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 batch disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of reserve 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.o 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.

4. Your firm failed to establish 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)).

You used water as a component to manufacture your OTC drug products. You were unable to provide adequate documentation demonstrating that your water system is validated. You failed to routinely monitor your (b)(4) water system for all required quality attributes to ensure that your water, at a minimum, meets the (b)(4) Water USP monograph and appropriate microbial limits. You lacked conductivity and total organic carbon limits and testing and did not test for specific objectionable microorganisms.

Your total microbial specification limit is (b)(4). This is above the appropriate limits for water intended for pharmaceutical manufacturing. Our inspection revealed at least one instance of elevated bioburden in 2024 (b)(4). These microorganisms were not further isolated to determine the identification of the bacterial species. Furthermore, your current schedule of quarterly microbiological testing is also insufficient.

The lack of data regarding the state of control of your water system poses a potential risk for 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 response to this letter, provide:

A comprehensive, independent remediation plan for the design, control, and maintenance of the water system.o A (b)(4) water system validation report specific for each water system in each building. Also include the summary of any improvements made to system design and to the program for ongoing control and maintenance for each water system.

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

A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.

The current action/alert limits for total counts and objectionable organisms used for your (b)(4) water system.

A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets (b)(4) Water, USP monograph specifications and appropriate microbial limits.

During the inspection, you provided a document indicating that you will discontinue manufacturing of various drug products and did not anticipate renewing your registration as an OTC drug manufacturer. We acknowledge your commitment to cease manufacturing of pain relief rubs and various hand sanitizer drugs. In response to this letter, clarify whether you intend to resume manufacturing any drugs for the U.S. market at this facility in the future.

If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPAs.

If your firm intends to resume manufacturing drugs for the U.S. market, 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.

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 reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3012853845 and ATTN: Jamie Dion.