R3 Medical Companies — FDA Warning Letter Findings

Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions, as required by 21 CFR 211.42(c)(10)(v). For example, you have not validated your processes for cleaning and disinfecting the ISO (b)(4) biological safety cabinet (BSC) where your products are exposed to the environment during aseptic processing.

Failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity that they are purported or represented to possess, as required by 21 CFR 211.100(a). For example, your firm has not validated the manufacturing processes for your umbilical cord derived products with respect to identity, strength, quality, and purity.

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.…

Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity, as required by 21 CFR 211.160(b). For example, samples of your umbilical cord derived products are frozen and thawed prior to sterility testing. Freezing samples has the potential to destroy or compromise any microbial content in the samples before testing, if present; therefore, any contamination that was present prior to freezing may not be reliably detected.

Failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes, as required by 21 CFR 211.113(b). For example, your firm has not validated the aseptic processes used to manufacture your umbilical cord derived products. Your umbilical cord derived products purport to be sterile and are expected to be sterile.