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January 23, 2014 Approval Order - CliniMACS CD34 Reagent System

Miltenyi Biotech, Inc.
Attention: Nancy Johansen
120 Presidential Way, Suite 305
Woburn, MA 01801

Re: HDE Number: BH110018
HUD Number: 04-0146
Device Name: CliniMACS® CD34 Reagent System
Filed: May 10, 2011
Amended: June 14, July 5, July 20, July 26, August 9, August 10, September 12, October 3, October 17, October 27, December 16, and December 28, 2011; May 29, June 7, July 16, July 23, and December 21, 2012; February 19, February 25, March 7, April 1, April 2, April 3, May 15, May 20, May 24, July 2, July 16, July 26, and December 3, 2013; January 2 and January 10, 2014
Product Code: OVG

Dear Ms. Johansen:

The Center for Biologics Evaluation and Research of the Food and Drug Administration (FDA) has completed its review of your humanitarian device exemption (HDE) application for the CliniMACS® CD34 Reagent System. This device is indicated for processing hematopoietic progenitor cells collected by apheresis (HPC, Apheresis) from an allogeneic, HLA-identical, sibling donor to obtain a CD34+ cell-enriched population for hematopoietic reconstitution following a myeloablative preparative regimen without the need for additional graft versus host disease (GVHD) prophylaxis in patients with acute myeloid leukemia (AML) in first morphologic complete remission.  We are pleased to inform you that your HDE is approved.  You may begin commercial distribution of the device in accordance with the conditions of approval described below.

The sale, distribution, and use of this device are limited to prescription use in accordance with 21 CFR 801.109 within the meaning of section 520(e) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) under the authority of section 515(d)(1)(B)(ii) of the FD&C Act. In addition, in order to ensure the safe use of the device, FDA has further restricted the device within the meaning of section 520(e) of the FD&C Act under the authority of section 515(d)(1)(B)(ii) of the FD&C Act insofar as the sale, distribution, and use must not violate sections 502(q) and (r) of the FD&C Act.

The components of the CliniMACS® CD34 Reagent System are the CliniMACS® CD34 Reagent, CliniMACS®plus Instrument (Model CS2-CE/UI), CliniMACS® Tubing Set (Standard (TS) or Large Scale (LS)), and CliniMACS® PBS/EDTA Buffer.  Expiration dating for the components and intermediates has been established and approved as follows:

  • Final Filled CliniMACS® CD34 Reagent: 18 months when stored at -70oC followed by 6 months when stored at 2-8oC
  • ----------------------------------------------(b)(4)-------------------------------------------------
  • ----------------------------------------(b)(4)--------------------------------------------
  • ------------------------(b)(4)------------------------------
  • CliniMACS® Tubing Set: 35 months from the date of sterilization 
  • CliniMACS® PBS/EDTA Buffer: 35 months from the date of sterilization


Continued approval of this HDE is contingent upon the submission of periodic reports, required under 21 CFR 814.126, at intervals of one year (unless otherwise specified) from the date of approval of the original HDE. Two (2) copies of this report, identified as "Annual Report"and bearing the applicable HDE reference number, should be submitted to the address below. The Annual Report should indicate the beginning and ending date of the period covered by the report and should include the information required by 21 CFR 814.126.

In addition to the above, an HDE holder is required to maintain records of the names and addresses of the facilities to which the HUD has been shipped, correspondence with reviewing institutional review boards (IRBs), as well as any other information requested by a reviewing IRB or FDA.

You have agreed to the following post-approval conditions:

Cleaning validation

1.  Miltenyi Biotec will use ------------(b)(4)------------- that meets -(b)(4)- specifications to repeat the cleaning validation for the multi-use product contact equipment used to manufacture CliniMACS CD34 Reagent System at Miltenyi’s Branch -(b)(4)-- Facility in --(b)(4)--.  Miltenyi Biotec will submit the results of the executed cleaning validation by June 30, 2014.

2.  Miltenyi Biotec will conduct periodic cleaning verifications to ensure that the cleaning procedures are still effective.  Miltenyi Biotec will submit the updated SOP documenting cleaning verification procedures by June 30, 2014.

---------(b)(4)------- testing of the CD34 Reagent

3.  Miltenyi Biotec will confirm the specificity/sensitivity of the commercial --(b)(4)------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ will be submitted by June 30, 2014.

4. Miltenyi Biotec will develop and validate a process-specific -----------(b)(4)-------------------- if the specificity/sensitivity of the ------------------(b)(4)------------------- cannot be adequately demonstrated. The final study and validation reports will be submitted by June 30, 2014.

Stability of the CD34 Reagent

5.  Miltenyi Biotec will submit annually the stability data from ongoing stability protocols for the --------------------------------------------(b)(4)-----------------------------------------------, and CliniMACS® CD34 Final Filled Reagent.  In addition, at least one commercial lot of each will be added to the stability program every year a lot is manufactured and these data will be submitted annually.

User Training

6.  Miltenyi Biotec will provide user training as described in SOP-1862 “Training of CliniMACS® Users (Customers) for Miltenyi Biotec Inc. (US)”.   Miltenyi Biotec will seek FDA approval prior to significant modification of this SOP and the user training program.

Before making any change affecting the safety or effectiveness of the device, you must submit an HDE supplement or an alternate submission (30-day notice) in accordance with 21 CFR 814.39 except a request for a new indication for use of for a humanitarian use device (HUD). A request for a new indication for use for an HUD shall comply with the requirements set forth in 21 CFR 814.110 which includes obtaining a new designation of HUD status for the new indication for use and submission of an original HDE application in accordance with §814.104. The application for the new indication for use may incorporate by reference any information or data previously submitted to the agency.

You are reminded that many FDA requirements govern the manufacture, distribution, and marketing of devices. For example, in accordance with the Medical Device Reporting (MDR) regulation, 21 CFR 803.50 and 21 CFR 803.52, you are required to report adverse events for this device. Manufacturers of medical devices, including in vitro diagnostic devices, are required to report to FDA no later than 30 calendar days after the day they receive or otherwise become aware of information, from any source, that reasonably suggests that one of their marketed devices:

1. May have caused or contributed to a death or serious injury; or

2. Has malfunctioned and such device or similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.

Additional information on MDR, including how, when, and where to report, is available at www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

In accordance with the recall requirements specified in 21 CFR 806.10, you are required to submit a written report to FDA of any correction or removal of this device initiated by you to: (1) reduce a risk to health posed by the device; or (2) remedy a violation of the act caused by the device which may present a risk to health, with certain exceptions specified in 21 CFR 806.10(a)(2). Additional information on recalls is available at www.fda.gov/Safety/Recalls/IndustryGuidance/default.htm.

This device may not be sold for an amount that exceeds the costs of research and development, fabrication, and distribution of the device. See section 520(m)(3) of the Federal Food, Drug, and Cosmetic Act.

Failure to comply with any post-approval requirement constitutes a ground for withdrawal of an HDE. The introduction or delivery for introduction into interstate commerce of a device that is not in compliance with its conditions of approval is a violation of law.

CBER does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. CBER will notify the public of its decision to approve your HDE by making available a summary of the safety and probable benefit of the device upon which the approval was based. The information can be found on the FDA CBER Internet Page located at http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/PremarketApprovalsPMAs
.Written requests for this information can also be made to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. The written request should include the HDE number or docket number. Within 30 days from the date that this information is placed on the Internet, any interested person may seek review of this decision by requesting an opportunity for administrative review, either through a hearing or review by an independent advisory committee, under section 515(g) of the FD&C Act.

You are reminded that, as soon as possible and before commercial distribution of your device, you must submit an amendment to this HDE submission with copies of all approved labeling in final printed form. The labeling will not routinely be reviewed by FDA staff when HDE applicants include with their submission of the final printed labeling a cover letter stating that the final printed labeling is identical to the labeling approved in draft form. If the final printed labeling is not identical, any changes from the final draft labeling should be highlighted and explained in the amendment. 

Any information to be submitted to FDA regarding this HDE should be submitted in triplicate, unless otherwise specified, to the address below and should reference the above HDE number to facilitate processing:

U.S. Food and Drug Administration
Center for Biologics Evaluation and Research
Attn: Office of Cellular, Tissue, and Gene Therapies
Document Control Center, HFM-99, Suite 200N
1401 Rockville Pike
Rockville, MD 20852-1448

If you have any questions concerning this approval order, please contact Candace Jarvis at (301) -827-6536

Sincerely yours,

Celia M. Witten, Ph.D., M.D.
Office of Cellular, Tissue and Gene Therapies
Center for Biologics Evaluation and Research

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