Advanced Nutriceuticals, LLC dba The Guyer Institute of Molecular Medicine — FDA Warning Letter Findings

Your response states that (b)(4) , but no further details about the kits were provided. It cannot be determined from the available information if the kits (b)(4) .

Your firm failed to retest or reexamine components, as appropriate, for identity, strength, quality, and purity and your quality control unit failed to approve or reject components (21 CFR 211.87). Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act…

Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).

Your response states that opened vials will (b)(4) from opening or the date of expiry and the vials will only be (b)(4) . Your response did not provide justification for (b)(4) . It is unclear if the stoppers for your stock vials, which are prepared in house, are intended for (b)(4) . Your response states that employees have been instructed to visually inspect stock solution vials. Visual inspection of (b)(4) vials is not a suitable indicator that the product remains sterile. Your response does not demonstrate how you will prevent contamination when (b)(4) , with or without use of (b)(4) , are stored outside of an ISO 5 environment.

Your personnel performing sterile operations have never conducted media fills. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.

Your firm failed to clean and sterilize and process, where indicated by the nature of the drug, container closures to remove pyrogenic properties to assure they are suitable for their intended use (21 CFR 211.94(c)).

Your response did not address the cleaning and mitigation of the visible drug residues on your current shared equipment that was observed during the inspection. Regarding your responses related to the insanitary conditions, the following corrective actions appear deficient…

Your aseptic processing and surrounding areas had difficult to clean and visibly dirty equipment or surfaces. For example: a. HEPA filters were discolored and/or damaged in the ISO 5 cleanroom hood. b. Your ISO 5 cleanroom workbench was constructed of laminated wood. c. A heating vent located below the ISO 5 cleanroom hood was visibly dirty and had no filtering device.

Your response states that (b)(4) building on the property. The response does not address how or if the current ISO 7/8 suite of rooms will be used in the future.

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

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)).

Your response states that you plan to (b)(4) , but intend to (b)(4) . However, no information was provided about the type of equipment and proposed timeline for this corrective action.

Your firm has not conducted environmental monitoring since 2018.

You committed to the cessation of pre-filling syringes for shipment to patients. Your response states that staff have been counseled and refresher training on proper aseptic technique would be completed, but no documentation related to this was provided.

Your firm failed to prepare batch production and control records for each batch of drug product that include documentation of the accomplishment of each significant step in the manufacture, processing, packing, or holding of the batch (21 CFR 211.188(b)).

Your response did not provide sufficient detail for an evaluation of your corrections related to the handling of hazardous drugs to prevent cross contamination.

Your firm uses (b)(4) drug product vials; however, your response states you are (b)(4) , which would not be suitable for use in (b)(4) . It is unclear whether your firm has purchased (b)(4) for sterilization of the product vials. Your response does not address the (b)(4) of product vials. You provided no information demonstrating that the current (b)(4) cycle is adequate. Your response does not address the use of (b)(4) during sterilization or (b)(4) during (b)(4) . The use…

Your response failed to address your lack of routine environmental monitoring.

Your personnel engaged in poor aseptic technique on multiple occasions during the processing of sterile drug products. For example: a. An operator placed their gloved hands outside the ISO 5 work area repeatedly to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood. b. An operator failed to sanitize or change gloves after contact with non-sterile materials (e.g., face mask, trash can) during sterile processing. c. An operator blocked first air by placing gloved hands directly in line with the sterile filter and open sterile containers.

Your response to multiple observations includes the creation or revision of procedures and/or personnel training. None of the pertinent documentation was provided.

Your “IV Hood” used to produce drug products purporting to be sterile is located in an unclassified room. In addition, this hood has not been certified in over two years.

Your response did not address what actions, if any, were taken to ensure the IV hood located in the unclassified room is no longer used.

Your firm handled hazardous drugs without providing adequate containment, segregation, or cleaning of work surfaces and utensils to prevent cross-contamination. Furthermore, the manufacture of the ineligible drug products is subject to FDA’s CGMP regulations, Title 21, Code of Federal Regulations (CFR), parts 210 and 211. The FDA investigators observed significant CGMP violations at your facility, causing the ineligible drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations included, for example…

Your firm compounded drug products using (b)(4) . Drug products compounded using (b)(4) , and (b)(4) are not eligible for the exemptions provided by section 503A(a), because (b)(4) , and (b)(4) are not the subject of an applicable USP or NF monograph, are not components of FDA-approved human drugs, and do not appear on the 503A bulks list. 2 Therefore, you compounded drug products that do not meet the conditions of section 503A and are not eligible for the exemptions in that…

Your operator engaged in aseptic processing while wearing non-sterile gloves, street clothes, and with exposed skin within the ISO 5 aseptic processing area.

Your response states your firm has implemented several corrections such as the (b)(4) , and (b)(4) . No supporting documentation was provided for those corrective actions. No additional information was provided related to the ISO 5 hood with the laminated work surface, which you stated you are (b)(4) .

Your response refers to staff members responsible for administering IVs being allowed to (b)(4) . It is unclear which staff members this refers to, where this operation is to occur, and whether those employees will also be conducting (b)(4) . You did not address certain observations related to insanitary conditions, for example…

Your firm failed to have buildings used in the manufacture, processing, packing, or holding of drug products of a suitable size, construction and location to facilitate cleaning, maintenance, and proper operations (21 CFR 211.42(a)).

Your firm did not receive valid prescriptions for individually-identified patients for a portion of the drug products you produced, such as your “ (b)(4) ” products, including Energy Boost.

Your response states that you would (b)(4) which would be more conducive to maneuvering in the cleanroom. It is unclear whether this is referring to (b)(4) to go inside the hood or beside the hood. If inside, dynamic smoke studies have not been provided to evaluate the effect of the (b)(4) on laminar airflow. If outside the hood, employees may continue to have issues reaching in and out of the hood to retrieve needed supplies during sterile operations.

Your operator was observed conducting aseptic operations outside of a certified ISO 5 area. The filling of sterile drug products into syringes, which were not for immediate administration to patients, but for shipment to patients across the country, was conducted in the unclassified dispensary area by personnel in street clothes with no gloves donned.

Your firm exposed a stock solution intended to be sterile to worse than ISO 5 air after the stopper had been punctured multiple times. Specifically, the stock solution was stored in an unclassified area for further use after the container closure system had been punctured multiple times, and therefore compromised, throughout the assigned expiry period.

Your firm failed to establish a system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).

Your response states you intend (b)(4) building which will include (b)(4) . No additional information or supporting documentation was provided regarding this renovation; no response updates have been received.

Your response states that (b)(4) units to be installed but does not address the (b)(4) monitoring in your current classified areas.

Your response did not address the lack of (b)(4) by your operators during aseptic production.

An operator was observed manually stoppering sterile drug vials and touching product contact surfaces during the process.

Your firm stores unused product vials in non-sterile plastic bags, which are allowed to be reused in sterile production. The vials stored in these bags are not (b)(4) . Moreover, your firm’s temperature and time conditions used for (b)(4) of product vials are not known to be (b)(4) microorganisms.