Findings citing 21 CFR 211.166

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 quality unit (QU) did not adequately oversee your drug manufacturing operations. For example, your QU failed to ensure: Adequate documentation of production and process control functions executed at the time of performance (21 CFR 211.100(b)) Adequate validation of manufacturing processes and the (b)(4) system (21 CFR 211.100(a) Adequate written procedures for production and process control (21 CFR 211.100(a)) Adequate stability testing program (21 CFR 211.166) Adequate finished product testing (21 CFR 211.165(a), 211.165(b)) Your firm’s quality systems are inadequate. See FDA’s guidance document ICH Q10 Pharmaceutical Quality System, as well as 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/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-system and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations, respectively. 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 Lot Identification CGMPs define a lot number, control number, or batch number as any distinctive combination of letters, numbers, or symbols, or any combination of them, from which the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot of drug product or other material can be determined. Upon further review of your records and information, it appears that you assign the same batch number to different products fulfilled on a single Purchase Order. You have identified drug products with different active ingredients, routes of administration, use instructions, and dates of manufacture with the same batch number. You must establish written procedures to apply unique identification of the drug product with a lot or control number that permits determination of the history of the manufacture and control of the batch. (21 CFR 211.130(c)). Drug Recall On February 3, 4, and 5, 2026, FDA attempted to contact you requesting a teleconference to discuss recalling your (b)(4) labeled as sterile, within expiry, and currently in distribution to the U.S. market. We have also attempted to contact your listed U.S. Agent. To date, neither you or your U.S. Agent have responded to any of our attempts for direct contact. We recommend you remove any batches of (b)(4) labeled as sterile currently in distribution and within expiry from the U.S. market. 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 evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. 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.

Your firm’s quality 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 establish an adequate QU with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure: Adherence to a stability program that supports the drug products’ expiration dating (21 CFR 211.166(a)). Contemporaneous documentation of EM and personnel monitoring sampling data in laboratory records (21 CFR 211.194(a)). In response to this letter, provide: A comprehensive 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 (ALCOA) records throughout your operation. A comprehensive assessment and remediation plan to ensure your QU is given the authority, independence, and resources to effectively function that includes, but is not limited to: o A determination of whether procedures used by your firm are robust and appropriate o Provisions for independent QU oversight throughout your operations to ensure satisfactory procedures and 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 o Also, describe how executive management will support robust quality assurance at your firm, including but not limited to timely provision of resources that enable proactive detection and resolution of emerging manufacturing/quality issues to assure a continuing state of control Ineffective Quality System Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements. Your firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidances: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download, Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download. Drug Production Ceased and Suspended We acknowledge your commitment to suspend production of (b)(4) Drugs at this facility for the U.S. market and to cease production of all other (b)(4) solutions. If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before 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 six-system audit 1 of your entire operation for CGMP compliance and evaluate the completion and efficacy of all CAPA, before you pursue resolution of your firm’s compliance status with FDA. 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. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA. Repeats Violation at Facility In a previous warning letter (WL 320-19-01), FDA cited similar CGMP violations. You proposed specific remediations for these violations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate. Additional Guidance on Aseptic Processing See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.

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 quality unit (QU) lacked adequate control over your OTC drug product manufacturing operations and failed to ensure that you had adequate procedures. Your firm made changes to your manufacturing process parameters in the batch manufacturing instructions without following your Procedure for Change Management and Operational Procedures for Handling of Abnormal Situations . For example: During the manufacture of your product (b)(4) , batch (b)(4) , you changed your (b)(4) without documented justification. During the manufacture of your product (b)(4) , batches (b)(4) , you changed a (b)(4) without documented justification. Your response states that a retrospective investigation revealed that your research and development team made on-site adjustments to process parameters without following the established change procedure. In your response you commit to following the required change procedure. Your response is inadequate because your retrospective review did not include a comprehensive assessment of other possible incidents of the change procedure not being followed. Additionally, the following are examples of poor QU oversight: The batch production and control records are deficient in that they do not include documentation of the accomplishment of each significant step in manufacturing. 21 CFR 211.188(b) There is no written testing program designed to assess the stability characteristics of drug products. 21 CFR 211.166(a) An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/downloads/drugs/guidances/ucm353925.pdf for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR parts 210 and 211 . In response to this letter, provide the following: A copy of your revised SOP, Operational Procedures for Handling of Abnormal Situations 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. Procedures to ensure if your manufacturing process parameters change your quality approves before all commercial manufacturing. Training records to confirm that all relevant personnel, including research and development staff have been trained in the change management requirements. Drug Production Suspended During the inspection you communicated your decision to allow your drug registration with the FDA to expire. Your firm stated that you will renew the drug registration if a U.S. (b)(4) order is received. If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before 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 six-system 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. 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. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).

Failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates, as required by 21 CFR 211.166(a). For example, your firm assigns a 24-month expiration date to your products without supporting stability testing data. The CGMP violations applicable to your Bello and Regen facilities pertaining to your products include, but are not limited to, the following: 7 6. The responsibilities and procedures applicable to the quality control unit are not in writing and fully followed, as required by 21 CFR 211.22(d). For example, at the time of the inspection, written procedures describing the responsibilities of the quality unit had not been established, including but not limited to, procedures for the approval or rejection of drug products (21 CFR 211.22(a)) and the handling of all written and oral complaints regarding a drug product (21 CFR 211.198(a)). Responses to the Form FDA-483 We have reviewed your responses to the Form FDA-483s issued to each of your Bello and Regen facilities dated January 08, 2026 and January 06, 2026, as well as your correspondence dated November 20, 2025, in detail. While you represented that you have implemented or plan to implement certain corrective actions, the described corrective actions are not adequate to remedy the violations noted above. For example, your responses do not address your continued distribution of your products or specific plans for disposition of the remaining inventory manufactured under the violative conditions outlined above. We note that certain corrective actions cannot be evaluated because they lack supporting documentation. Further, for your previously distributed products, you do not describe actions you have taken or plan to take that adequately address the impact of the above-noted deficiencies on your distributed products that are still within expiry and were manufactured under the above-described violative conditions. We acknowledge your commitment to temporarily suspend manufacturing operations until you have made corrections to the observations listed on the Form FDA-483 issued to each of your Bello and Regen facilities. However, this does not resolve the violations outlined in this letter because your responses do not adequately address your failure to have an Investigational New Drug (IND) in effect to study your products addressed in this letter or your lack of an approved BLA to lawfully market your products. FDA has previously provided notice to you, David Greene, in a letter dated May 28, 2019, that based on a review of your website for R3 Stem Cell, LLC (www.r3stemcell.com) at that time, your firm appeared to offer “regenerative stem cell therapies” while promoting these stem cell therapies for numerous diseases or conditions, such as amyotrophic lateral sclerosis (ALS), diabetes, kidney failure, Lyme disease, Parkinson’s disease, and stroke. Based on that review, R3 Stem Cell, LLC did not appear to qualify for any exception under 21 CFR 1271.15; the “regenerative stem cell therapies” were intended for nonhomologous uses and thus would be regulated as drugs as defined in section 201(g) of the FD&C Act [21 U.S.C. 321(g)] and biological products as defined in section 351(i) of the PHS Act [42 U.S.C. 262(i)]. However, our review of your current websites and various social media accounts, which are also linked to your websites, indicates umbilical stem cell therapy and exosome therapy continue to be offered by R3 Stem Cell, LLC for treatment of various diseases and conditions, as described above. Additional Concerns In addition to the violations described above, we have the following concerns: FDA’s review of information and records collected during the inspections documented Bello also manufactures the following umbilical cord derived 8 products: BelloWJ, BelloXO, and BelloXOL. Your response dated January 08, 2026 asserts that Bello is a manufacturer of HCT/Ps and is subject only to current good tissue practice (CGTP) requirements of 21 CFR Part 1271 and is regulated solely under section 361 of the PHS Act); however, review of the evidence collected shows these products do not appear to meet the relevant criteria to be regulated solely under section 361 of the PHS Act, for the reasons discussed above. These products appear to be drugs and/or biological products, which are subject to premarket review and approval requirements. FDA review of Bello’s manufacturing records revealed that (b)(4) is a component of the (b)(4) used during Bello’s manufacturing process of products derived from umbilical cord tissue; however, there did not appear to be evidence that testing for (b)(4) had been performed prior to the release of these products, as required by (b)(4) . Bello determines donor eligibility upon review of relevant medical records per your contract agreement with (b)(4) . The “ Donor Eligibility Criteria ” documents (effective date 08/15/2023) submitted with your January 8, 2026, response and also collected during the inspection do not include “qualifiers/comments” for Transmissible Spongiform Encephalopathy (TSE). In accordance with 21 CFR 1271.75(a)(1)(iv), all donors of cells or tissues, except as provided under 1271.90, must be screened by reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases, including human transmissible spongiform encephalopathy, including Creutzfeldt-Jakob disease.…

Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (21 CFR 211.166(a)). Your firm has not established stability indicating methods for the OTC (b)(4) drug products you distribute to the U.S. market. For example, the validation protocol for the assay of Naphazoline HCl (NPZ) in the (b)(4) formulation detailed a stress study; however, the report stated that the stress study would be performed later and reported separately. Assay for NPZ is a test conducted for stability studies of the (b)(4) formulation. Without forced degradations studies to establish specificity, the accuracy of the test assay results cannot be assured throughout the shelf-life of the product during stability. In your response, you acknowledge that initial forced degradation studies for the current OTC (b)(4) formulations could not be located, and you commit to repeating these studies and creating an action plan based on the results. In addition, you commit to conducting a three-year retrospective review for the active pharmaceutical ingredient (API) testing during stability for each product code and to conducting a review of prior annual product reviews to evaluate any stability trends observed for the API and preservative systems for each product code. Proper document control and data management is foundational to CGMP to ensure the availability and integrity of data. Data should be attributable, legible, contemporaneously recorded, original or a true copy, and accurate (ALCOA) to ensure complete and accurate records. Your response is inadequate. Your review of retrospective data using methods that have not been validated as stability indicating provides insufficient confidence in your marketed drug products. Upon development of your stability indicating methods, you should add additional batches to your stability program, including retains of older batches (e.g., (b)(4) ). You did not assess the impact of inadequate stability testing and the potential for degradation products in OTC (b)(4) drug products within expiry distributed to the U.S. market. In response to this letter, provide: A comprehensive independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system. A comprehensive independent assessment and 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 whether the shelf-life claim remains valid o Detailed definition of the specific attributes to be tested at each station (timepoint), as part of a program that encompasses each quality attribute that may change over the product shelf-life. o All procedures that describe these and other elements of your remediated stability program. A commitment to notify FDA within 3 days of any stability failures.

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 establish an adequate QU with the responsibilities and authority to oversee the manufacturing of drug products. For example, the QU failed to ensure: Establishment of appropriate written procedures for production and process controls, including appropriate qualification of the (b)(4) system (21 CFR 211.100(a)). Establishment of an appropriate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)). Establishment of adequate written procedures defining QU responsibilities and controls (21 CFR 211.22(d)). An adequate number of qualified personnel to perform and supervise the manufacturing, processing, packing, or holding of each drug product (21 CFR 211.25(c)). Your firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA’s guidance documents Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download, Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download, and ICH Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/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. 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 evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA before you pursue resolution of your firm’s compliance status with FDA. 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 Listing Violations Section 510(j) of the FD&C Act and 21 CFR Part 207 set forth the requirements for the listing of drugs. In addition to listing a drug that you manufacture under your own labeler code, under 21 CFR 207.41(c)(1), you are required to list each drug you manufacture for commercial distribution under the trade name or label of a PLD using an NDC that includes such PLD’s labeler code. Evidence from the most recent inspection of your site and a search of eDRLS confirms that you are manufacturing KleenLine Alcohol-Free Sanitizing Wipes for a PLD, Brady Industries, Inc., but you did not list this drug under the PLD’s trade name and labeler code as required. Therefore, you failed to fulfill your drug listing obligations in accordance with section 510 of the FD&C Act. Failure to provide listing information for a drug in accordance with 510(j) of the FD&C Act is prohibited under section 301(p) of the FD&C Act. Under section 502(o), a drug is misbranded if it is not included in a list required by section 510(j). Under section 301(a), the introduction or delivery for introduction, or the causing thereof, into interstate commerce of any drug that is misbranded is prohibited. Complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance. Establishment registration and drug listing information is also widely used outside FDA for purposes such as electronic prescribing and electronic health records, insurance reimbursement, and patient education. We note that the labeling provided in your drug listing for Hand Sanitizing Alcohol-Free Wipes, NDC 84111-000, bears the trade name of what appears to be another PLD. Please update your labeling accordingly. It is your responsibility to ensure that all drugs manufactured at your establishment comply with all establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions .