Title

Bone marrow concentrate (BMC) therapy in musculoskeletal disorders: Evidence-based policy position statement of American Society of Interventional Pain Physicians (ASIPP)

Authors

Laxmaiah Manchikanti, University of Louisville
Christopher J. Centeno, Centeno-Schultz Clinic
Sairam Atluri, Tri-State Spine Care Institute
Sheri L. Albers, Radiology Research and Consultation
Shane Shapiro, Mayo Clinic in Jacksonville, Florida
Gerard A. Malanga, Rutgers New Jersey Medical School
Alaa Abd-Elsayed, University of Wisconsin School of Medicine and Public Health
Mairin Jerome, Interventional Orthopedics Foundation
Joshua A. Hirsch, Massachusetts General Hospital
Alan D. Kaye, LSU Health Sciences Center - Shreveport
Steve M. Aydin, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Douglas Beall, Clinical Radiology of Oklahoma
Don Buford, The Texas Orthobiologic Institute
Joanne Borg-Stein, Harvard Medical School
Ricardo Buenaventura, Pain Relief of Dayton
Joseph A. Cabaret
Aaron K. Calodney, Scott and White
Kenneth Candido, Advocate Aurora HealthFollow
Cameron Cartier, Anesthesiologist/Pain Medicine Physician
Richard Latchaw, Radiology Research and Consultation
Sudhir Diwan
Ehren Dodson, Regenexx, LLC
Zachary Fausel, Centeno-Schultz Clinic
Michael Fredericson, Stanford University
Christopher G. Gharibo, NYU Langone Orthopedic Hospital
Mayank Gupta, Neuroscience Research Center, LLC
Adam M. Kaye, University of the Pacific, California
Nebojsa Nick Knezevic, Advocate Aurora HealthFollow
Radomir Kosanovic, Pain Management Centers of America
Matthew Lucas, Interventional Spine and Sports Medicine
Maanasa V. Manchikanti, University of Kentucky
R. Amadeus Mason, Emory University School of Medicine
Cyril Philip, Advocate Aurora HealthFollow

Affiliations

Advocate Illinois Masonic Medical Center.

Abstract

Background: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine.

Objectives: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around "minimal manipulation" and "homologous use" within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine.

Methods: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980's and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA's intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs.

Conclusions: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use.

Document Type

Article

PubMed ID

32214287

Link to Full Text

 

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