Microvascular Tissue, Inc.

The United States Food and Drug Administration (FDA) inspected your facility, located at the above address, between March 31, 2025, and April 8, 2025. During the inspection, FDA documented that your company markets and distributes a product derived from hypodermis that you recover from donors, and marketed as mVASC® (hereinafter, “mVASC” or “your product”), for allogeneic use. Your firm has a contract with (b)(4), for them to manufacture mVASC and you also participate in its manufacture.

This letter is to advise you that your product is an unapproved new drug in violation of section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C § 355(a). Your product is also an unlicensed biological product in violation of section351(a)(1) of the Public Health Service Act (PHS Act), 42 U.S.C. § 262(a)(1). A biological product for which a biologics license application (BLA) has been approved under section 351(a) of the PHS Act is not required to have an approved application under section 505 of the FD&C Act, 21 U.S.C. § 355; 42 U.S.C. § 262(j). Otherwise, with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act. Your introduction or delivery for introduction of your product into interstate commerce, or the causing thereof, is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. § 331(d).

This warning letter also summarizes significant violations of current good manufacturing practice (CGMP) requirements, including violations of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. § 351(a)(2)(B), and 21 CFR parts 210 and 211 in the manufacture of your product. Because your methods, facilities, or controls for manufacturing, processing, packing, or holding drugs do not conform to CGMP, your product is adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. § 351(a)(2)(B). Your introduction or delivery for introduction of your product into interstate commerce, or the causing thereof is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C. § 331(a).

Based on information and records reviewed by FDA, including your website, www.mvtissues.com, last visited December 2025, your product is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease or conditions in humans and/or are intended to affect the structure or function of the body. For example:

Your website states that “mVASC is intended for the repair, reconstruction, replacement, or supplementation of damaged extracellular matrix (ECM) in skin defects that extend through the dermis into and/or through the hypodermis.”

Your website’s title tag states, “MicroVascular Tissues – Healing Vascular Deficiences [sic].”

Your tissue distributor training presentation titled “mVASC Wound Applications”, dated March 2025 states, “mVASC healed 74% of DFUs [Diabetic Foot Ulcers] at 12 weeks versus 38% for SOC [Standard of Care].”

Therefore, your product is a drug as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and a biological product as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i).

Your product is also a human cell, tissue, or cellular or tissue-based product (HCT/P) as defined in 21 CFR 1271.3(d) and is subject to regulation under 21 CFR part 1271, issued under the authority of section 361 of the PHS Act, 42 U.S.C. § 264. HCT/Ps that do not meet all the criteria in 21 CFR 1271.10(a) are not regulated solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271. Unless an exception in 21 CFR 1271.15 applies, such products are regulated as drugs, devices, and/or biological products under the FD&C Act and/or the PHS Act and are subject to additional regulation, including applicable premarket review. Based on a review of relevant materials, Microvascular Tissues, Inc. does not qualify for any exception in 21 CFR 1271.15, and your product fails to meet all criteria in 21 CFR 1271.10(a).

Because the hypodermis that you recover from donors is predominantly composed of adipocytes and surrounding connective tissues that mainly function to provide physical cushioning and support to the body, FDA considers the hypodermis to be a structural tissue for the purpose of applying the regulatory framework. Under the 21 CFR part 1271 regulatory framework, a structural tissue is minimally manipulated if the processing does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement. 21 CFR 1271.3(f)(1). Thus, whether processing of hypodermis would meet the regulatory definition of minimal manipulation takes into consideration whether the processing alters the original relevant characteristics of the hypodermis related to its utility to provide cushioning and support to the body.

Your product fails to meet the minimal manipulation criterion set forth in 21 CFR 1271.10(a)(1) and defined for structural tissue in 21 CFR 1271.3(f)(1), because your processing alters the original relevant characteristics of hypodermal tissue related to its utility for reconstruction, repair, or replacement. Hypodermis tissue (i.e., subcutaneous layer comprising adipose tissue) is processed by your firm using (b)(4).1 (b)(4), thus altering the structure of the extracellular matrix.

In addition, your mVASC product fails to meet the criterion that the HCT/Ps be “intended for homologous use only.” Homologous use means that the “labeling, advertising, or other indications of the manufacturer’s objective intent” demonstrate that the HCT/P is intended to perform “the same basic function or functions in the recipient as in the donor.” 21 CFR 1271.3(c) & 1271.10(a)(2). Your hypodermis (i.e., subcutaneous layer comprising adipose tissue) derived ECM product is not intended to perform the same basic function or functions in the recipient as in the donor (e.g., providing cushioning and support to the body). Rather, the use of your product for repair, reconstruction, replacement, or supplementation of damaged ECM in skin defects that extend through the dermis into and/or through the hypodermis is not a basic function of hypodermis in the donor (e.g., providing cushioning and support to the body). In contrast to that basic function, mVASC is instead intended to facilitate the healing of full thickness skin wounds via revascularization which would require the biochemical stimulation of a wound healing response in the body via cell signaling. This is a non-homologous use for hypodermis tissue.

Therefore, this HCT/P is not regulated solely under section 361 of the PHS Act, 42 U.S.C. § 264, and the regulations in 21 CFR part 1271.2 See 21 CFR 1271.20. In addition to being regulated under section 361 of the PHS Act and 21 CFR part 1271, your product is regulated as a drug as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and a biological product as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i), as stated above.

Subject to certain exceptions not applicable here, to lawfully introduce or deliver for introduction into interstate commerce a drug that is a biological product, a valid BLA must be in effect under section 351(a)(1) of the PHS Act, 42 U.S.C. § 262(a)(1). Such licenses are issued only after showing that the product is safe, pure, and potent. Your product is not the subject of an approved BLA.

FDA’s inspection of your facility documented evidence of significant CGMP violations. At the conclusion of the inspection, FDA investigators issued a Form FDA-483, List of Inspectional Observations (Form FDA-483).

The CGMP violations applicable to your product include, but are not limited to, the following:

1. Failure to establish adequate written procedures for production and process controls designed to assure that the drug products have the identity, strength, purity, and quality that they are purported or represented to possess, as required by 21 CFR 211.100(a). You have not validated the manufacturing process for your product with respect to identity, strength, quality, and purity. For example:

a. Your firm has not validated critical manufacturing steps for your product, including the (b)(4) using (b)(4) with the (b)(4).b. Your firm has not performed a process validation since moving the “(b)(4)” to a new contract manufacturer in November 2018.

2. Failure to conduct at least one test to verify the identity of each component of a drug product, using specific identity tests if they exist, as required by 21 CFR 211.84(d)(1). Identity testing is not performed on each component used in the manufacturing of mVASC, for example (b)(4).

We have reviewed your response, dated April 29, 2025, to FDA’s Form FDA-483 in detail. Your response is inadequate to address the violations noted above. For example, your response does not adequately address your firm’s continued manufacture and distribution of your product or your plans for disposition of your current inventory manufactured under the violative conditions outlined above. Additionally, 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 product that carries an (b)(4) shelf life and was manufactured under the above-described conditions.

Your firm’s response repeatedly asserts that your product should be regulated solely under section 361 of the PHS Act, and that the violations noted above are not applicable to your product. Based on your position, you have not adequately proposed corrective actions which address the CGMP violations noted above. While you assert that your product should be regulated solely under section 361 of the PHS Act, as explained above, the available evidence shows that your product does not meet all criteria in 21 CFR 1271.10(a) for regulation solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271.

As such, your response further does not adequately address your lack of an approved BLA to lawfully market your product. As noted above, to lawfully market a drug that is a biological product, a valid biologics license must be in effect. 42 U.S.C. 262(a). Such licenses are issued only after showing that the product is safe, pure, and potent.

Neither this letter nor the observations noted on the Form FDA-483, which were discussed with you at the conclusion of the inspection, are intended to be an all-inclusive list of deficiencies that may exist in connection with your product. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure full compliance with all applicable requirements in the FD&C Act, PHS Act, and all applicable regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address these matters may result in action without further notice including, without limitation, seizure and/or injunction.

Send your electronic response and any questions regarding this letter to CBER’s Office of Compliance and Biologics Quality, Division of Case Management at CBERDCMRecommendations@fda.hhs.gov.