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The regulations behind our services

Biologics under FDA guidelines.

Since the inception of Boulder Biologics, we have prioritized compliance with FDA guidelines. The regenerative medicine space has rapidly evolved in the last several years, and the FDA guidelines have also been further clarified. Our approach has always been to optimize the safety and efficacy of the therapeutics we offer while adhering to the rules set forth.

Key FDA definitions

HCT/Ps and the regulatory vocabulary.

Human cells, tissues, and cellular and tissue-based products (HCT/Ps) comprise human cells or tissues intended for implantation, transplantation, infusion, or transfer into a human recipient. The pertinent FDA definitions follow.

Structural Tissues

FDA classification

Tissues that physically support or serve as a barrier or conduit, or connect, cover or cushion in the donor are generally considered structural tissues for the purposes of determining the applicable regulatory definition. Examples of structural tissues include bone, skin, amniotic membrane and umbilical cord, blood vessel, adipose tissue, articular cartilage, non-articular cartilage, and tendon or ligament.

Cells and Nonstructural Tissues

FDA classification

Cells or nonstructural tissues are generally those that serve predominantly metabolic or other biochemical roles in the body, such as hematopoietic, immune, and endocrine functions. Examples of nonstructural tissues include reproductive cells or tissues, hematopoietic stem/progenitor cells, lymph nodes and thymus, parathyroid glands, peripheral nerve, and pancreatic tissue.

Minimal Manipulation

21 CFR 1271.1(f)
  • Structural tissue: processing that does not alter the original relevant characteristics of the tissue relating to the tissue's utility for reconstruction, repair, or replacement.
  • Cells or nonstructural tissues: processing that does not alter the relevant biological characteristics of cells or tissues.

Homologous Use

21 CFR 1271.3(c)

The repair, reconstruction, replacement, or supplementation of a recipient's cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.

Same Surgical Procedure Exception

21 CFR 1271.15(b)

For the exception to apply, an establishment must:

  • Remove and implant the HCT/Ps into the same individual from whom they were removed (autologous use).
  • Implant the HCT/Ps within the same surgical procedure.
  • The HCT/Ps remain "such HCT/Ps;" they are in their original form. Generally, to remain "such HCT/Ps," the only processing steps are rinsing, cleansing, sizing, and shaping.

Section 361 of the PHS Act & 21 CFR 1271.10(a)

Why our clinical cellular therapies require no FDA approval.

Clinical cellular therapies performed at Boulder Biologics are regulated solely as HCT/Ps and require no FDA approval given that they meet section 361 of the PHS Act and the CFR 1271.10(a) criteria:

  1. The HCT/P is minimally manipulated.
  2. The HCT/P is intended for homologous use only, as reflected by the labeling, advertising, or other indications of the manufacturer's objective intent.
  3. The manufacture of the HCT/P does not involve the combination of the cells or tissues with another article, except for water, crystalloids, or a sterilizing, preserving, or storage agent, provided that the addition of water, crystalloids, or the sterilizing, preserving, or storage agent does not raise new clinical safety concerns with respect to the HCT/P.

And either:

  • The HCT/P does not have a systemic effect and is not dependent upon the metabolic activity of living cells for its primary function, or
  • The HCT/P has a systemic effect or is dependent upon the metabolic activity of living cells for its primary function, and is for autologous use, allogeneic use in a first-degree or second-degree blood relative, or reproductive use.

In practice

Boulder Biologics is an FDA guideline–compliant provider.

The Boulder Biologics lab processes ex vivo cell products used in humans, which are defined as "minimally manipulated" by FDA categorization. It follows the current Good Tissue Practice (cGTP) guidelines as described in the Code of Federal Regulations (CFR) title 21, part 1271. The ex vivo cell products are obtained from the patient (autologous) and include whole blood, bone marrow aspirate, and adipose for orthopedic joint-related procedures. The FDA-defined structural and cell/nonstructural products used at Boulder Biologics are:

  • Structural: autologous adipose
  • Nonstructural / Cell: autologous bone marrow aspirate

Cellular therapies are processed at Boulder Biologics using minimal manipulation in accordance with 21 CFR 1271.1(f). Processing includes concentrating blood and bone marrow aspirate using density-gradient centrifugation. The processing of blood requires the use of the anticoagulant ACD-A. Bone marrow aspirate requires a small amount of the anticoagulant heparin and ACD-A to be used during the harvest and processing stages. Bone marrow used for infusion or for concentrating for injection is passed through a sterile filter.

Adipose tissue harvested for orthopedic procedures undergoes a short centrifugation process to remove excess saline used in the harvest infiltration process. Adipose-based cellular therapy is only employed for orthopedic treatment by injection. Adipose has never been utilized at Boulder Biologics for intravenous infusion, intranasal delivery, or any medical cellular therapy procedure, nor has it ever been implied to patients that we perform adipose-based tissue/cellular treatments for intravenous infusion or intranasal administration.

Cellular and tissue therapies at Boulder Biologics are all performed under homologous use, 21 CFR 1271.3(c). All cellular and tissue therapies are also harvested, processed, and applied during the same procedure; therefore, the same surgical procedure exception in 21 CFR 1271.15(b) applies, and the requirements in 21 CFR Part 1271 are not applicable.

Any individual(s) or other entity that engages in statements that contradict that which is stated above may be viewed as defamation per se (re. individual employees) or as trade libel (re. Boulder Biologics, LLC) and is subject to legal action.

References

FDA source documents.

  1. Regulatory considerations for human cells, tissues, and cellular and tissue-based products: minimal manipulation and homologous use. U.S. Food and Drug Administration. fda.gov/regulatory-information/...minimal
  2. Same surgical procedure exception under 21 CFR 1271.15(b): questions and answers regarding the scope of the exception. U.S. Food and Drug Administration. fda.gov/media/89920/download
  3. Regulatory considerations for HCT/Ps: minimal manipulation and homologous use, guidance for industry and FDA staff. U.S. Food and Drug Administration. fda.gov/media/109176/download
  4. 21 CFR Part 1271 Subpart D, Current Good Tissue Practice. Electronic Code of Federal Regulations. ecfr.gov/current/title-21/.../subpart-D

Schedule a consultation

Questions about our process or compliance posture?

Dr. Glowney and the team are happy to walk you through how we harvest, process, and deliver autologous biologic material, and how that aligns with current FDA guidance.

Or call 720-550-6175
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