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  6. map3 Chips Allograft-Untitled Letter
  1. Enforcement Actions (CBER)

map3 Chips Allograft-Untitled Letter

VIA FACSIMILE AND UPS

Brian Hutchison
ChiefExecutive Officer
RTI Surgical, Inc.
11621 Research Circle
Alachua, FL 32615-6825

Dear Mr. Hutchison:

During an inspection of your firm, RTI Surgical, Inc., located at 4 Pearl Court, Suite C, Allendale, NJ 07401, from December 3, 2013, to January 9, 2014, the Food and Drug Administration (FDA) collected information regarding the manufacture of your bone marrow­ derived multipotent adult progenitor cells  for the map3™ cellular allogeneic bone graft kit (map3™ Chips Allograft).  The map3™ Chips Allograft is used for the repair, replacement or reconstruction of bony defects by a qualified healthcare professional (e.g., physician or podiatrist).

Your map3™ Chips Allograft consists of a scaffold composed of demineralized bone matrix and cortical cancellous chips, as well as cultured bone marrow-derived multipotent adult progenitor cells , cryopreserved in a suspension. All these constituents are processed from the same human donor. The final packaged product includes the demineralized bone matrix, cortical cancellous chips and the multipotent adult progenitor cells.

RTI Surgical in Alachua, Florida (RTI, FL) ---------------------(b)(4)------------------------------------------------------.  RTI Surgical in Allendale, New Jersey (RTI, NJ) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------(b)(4)-------------------------------------------------------------------------------------.

Your map3™ Chips Allograft cultured cell product is a human cell, tissue, or cellular or tissue­based product (HCT/P) as defined in 21 CFR 1271.3(d), and is subject to regulation under 21 CFR Part 1271, issued under authority of section 361 ofthe  Public Health Service Act (PHS Act
(42 U.S.C. 264]).  HCT/Ps that do not meet all of the criteria in 21 CFR 1271.10(a), are subject to additional regulation, including appropriate premarket review.

The multipotent adult progenitor cells included as a component in map3™ Chips Allograft do not meet all of the criteria in 21 CFR 1271.1 O(a), and therefore the product is not regulatedsolely under section 361 of the Public Health Service Act (PHS Act) [42 U.S.C. 264] and the regulations in 21 CFR Part 1271. Specifically, your process of ------------------------------------------------------------------------------(b)(4)--------------------------------------------------------------------------------------------, alters the relevant biological characteristics of the cells.  Therefore, your processing does not meet the definition of minimal manipulation for cells or nonstructural tissues established in 21 (1271.3(f)(2)),  and neither the multipotent adult progenitor cells, nor the final map3™ Chips Allograft, meet the criterion in 21 CFR 1271.10(a)(l).

In addition, based on information provided on your website: http://www.map3bonegraft.com/why-map3,the multipotent adult progenitor cells, "provide a unique set of angiogenic cytokines that affect the regulation and differentiation of vascular endothelial cells, thus promoting the growth of new blood vessels."  Therefore, these multipotent adult progenitor cells are dependent on the metabolic activity of living cells for their primary function.  This cellular product is not intended for autologous use or allogeneic use in a first or second degree blood relative; accordingly it does not meet the criterion in 21 CFR
1271.1O(a)(4)(ii)(b).

Because they do not meet the criteria in 1271.1 O(a), the multipotent adult progenitor cells and the map3™ Chips Allograft product are subject to additional regulation as drugs as defined under section 201(g) of the Federal Food, Drug, and Cosmetic Act (the 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)].

Please be advised that in order to lawfully market a drug that is also a biological product, a valid biologics license must be in effect [42 U.S.C. 262(a)]. Such licenses are issued only after a demonstration that the product is safe, pure, and potent. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug (IND) application  in effect as specified by FDA regulations (21 U.S.C. 355(i); 42 U.S.C. 262(a)(3); 21 CFR Part 312). Your map3™ Chips Allograft is not the subject of an
approved biologics license application (BLA) nor is there an IND in effect. Based on this information, we have determined that your actions have violated the Act and the PHS Act.

Additionally, it appears that your firm is not performing all of the necessary donor testing for the bone marrow component  of your product.  You must test a specimen from the donor of viable, leukocyte-rich cells or tissue for evidence of infection due to cytomegalovirus (CMV), to adequately and appropriately  reduce the risk of transmission. You must establish and maintain a standard operating procedure governing the release of an HCT/P from a donor whose specimen tests reactive for CMV (1271.85).

This letter addresses certain issues for the multipotent adult progenitor cells included in the map3™ Chips Allograft, and is not intended to be an all-inclusive review of the products that your firm markets.  It is your responsibility to ensure that all products marketed by your firm are in compliance with the Act and the PHS Act and their implementing regulations.

We request that you notify this office, in writing, of the steps you have taken or will take to address the violations noted above and to prevent their recurrence. Your response should be sent to me at the following address:  U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, 10903 New Hampshire Avenue, Bldg. 71, Silver Spring, MD 20993.

If you have any questions regarding this matter, you may contact the Division of Case Management at (240) 402-9155. Please be advised that only written communications are considered official.
 

Sincerely,

Mary A. Malarkey
Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research

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