Frequently Asked Questions (FAQs)for requesting stem cell lines made by the Regenerative Medicine Program

 

  1. What types of stem cell lines are available from the Regenerative Medicine Program (RMP)?

    There are 14 research grade induced pluripotent stem cell (iPSC) lines generated by the RMP available to the scientific community through Rutgers University’s RUDCR Infinite Biologics. A brief description of available iPSCs, along with publications using these cells, can be found on the RMP program resources website. Researchers can use this link to request these RMP research grade iPSC lines.

    There is one cGMP iPSC clinical grade stem cell line generated by the RMP available to the scientific community. Additional information about this line is provided in the remaining FAQs below. The cGMP iPSC clinical grade and corresponding research grade iPSC line generated by the RMP are stored and distributed through Rutgers University’s RUCDR Infinite Biologics. Researchers can use this link to request the cGMP iPSC clinical grade line (i.e. MCB) and corresponding research grade iPSC line (i.e. WCB) generated by the RMP.

  2. What is the difference between the cGMP iPSC master cell bank (MCB) and the iPSC working cell bank (WCB)?

    The cGMP iPSC MCB was generated by Lonza Walkersville from CD34+ cord blood using – and is being stored under – current Good Manufacturing Practices (cGMP) which is a requirement if iPSCs are to be used in clinical studies, as is the intention of these cells. The iPSC WCB (also generated by Lonza Walkersville) is a matched research grade iPSC bank developed from the MCB. After the MCB was derived and certified as cGMP, a vial of MCB was expanded under non-cGMP condition at Lonza process development laboratory to generate the WCB. The WCB was generated for researchers to develop and optimize protocols and standard operating procedures, such as evaluating differentiation potential, before requesting the MCB. The costs and specialized facilities necessary to generate and maintain cGMP iPSC cells necessitates that they only be used once procedures have been optimized and streamlined for clinical studies to prevent waste of precious resources. The generation of the cells is described in the following publications:

    Baghbaderani BA, Syama A, Sivapatham R, Pei Y, Mukherjee O, Fellner T, Zeng, Rao MS. Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications. Stem Cell Rev. 2016 Jun 10.
    Baghbaderani BA, Tian X, Neo BH, Burkall A, Dimezzo T, Sierra G, Zeng X, Warren K, Kovarcik DP, Fellner T, Rao MS. cGMP-Manufactured Human Induced Pluripotent Stem Cells Are Available for Pre-clinical and Clinical Applications. Stem Cell Reports. 5:647-659, 2015 Oct 13

  3. How do I obtain the cGMP iPSC master cell bank (MCB)?

    The costs and specialized facilities necessary to generate and maintain cGMP iPSC cells necessitates that they only be used once procedures have been optimized and streamlined for clinical studies. Thus, cGMP iPSCs are only needed in the late stage of a therapeutic development project when the requester is ready to start testing the therapy in humans. To ensure that only serious and properly prepared investigators receive the cGMP iPSC line requesters will need to demonstrate proof of a pre-Investigational New Drug meeting with the FDA related to the program for which the cells are sought or a letter of cross-reference for the Drug Master File (see number 7 below). View a flow chart of the procedure for obtaining the iPSC WCB and the iPSC MCB. The MCB is stored and distributed through Rutgers University’s RUCDR Infinite Biologics. Researchers can use this link to request the cGMP iPSC clinical grade line (i.e. MCB) and corresponding research grade iPSC line (i.e. WCB) generated by the RMP.

  4. How many cells are included with each request?

    One vial of cells, approximately 1-2 X 10^6 cells, is shipped to the requester.

  5. What documents are included with the iPSC working cell bank (WCB)? What about the cGMP iPSC master cell bank (MCB)?

    Documents included with the WCB
    • Certificate of Analysis
    • Tissue sourcing document with copy of IRB approval (covers MCB & WCB)
    • Material Transfer Agreement for WCB
    • End-user agreements document*
    • Instructions for culturing
    Documents included with the WCB
    • Official Certificate of Analysis
    • Tissue sourcing document with copy of IRB approval (covers MCB & WCB)
    • Material Transfer Agreement for MCB
    • End-user agreements document*
    • Data Package containing additional characterization data
    *The end-user agreement document was approved by iPSC Academia Japan, Inc., the company who holds the iPSC intellectual property patents used to generate the MCB and WCB. Obligations required by the document apply to requestors who receive WCB and MCB cells from Rutgers.

  6. Where can I obtain the intellectual property (IP) license requirements for the method(s) to induce pluripotency?

    The MCB and WCB cells were manufactured by Lonza Walkersville, a component of Lonza Group, Ltd. under a contract with NIH, using technology licensed from iPS Academia Japan, Inc. (IPSAJ), the holding company of iPSC intellectual property patents developed by Nobel Laureate Shinya Yamanaka at Kyoto University. Researchers wishing to use the cGMP iPSCs should read closely the end-user agreement document included with the cells and consult the IPSAJ license policy: http://ips-cell.net/e/license/policy.html. Lonza is also required to state that additional licenses may be needed by third-parties who receive the MCB line but that Lonza is not required to enforce those licenses. Other groups holding iPSC patents (besides ISPAJ) might assert their patent rights. Each Party receiving the MCB should conduct their own due diligence to determine if their actions or products have freedom to operate.

  7. Which organization submitted the Drug Master File (DMF) and can I obtain a letter of cross-reference for the DMF?

    Lonza has deposited the DMF with the Food and Drug Administration (FDA). To obtain a letter of cross-reference to the DMF please fill out the MF Cross Reference Request Template provided by Lonza making sure to follow the instructions provided in the Master File Access Request pfd, also provided by Lonza.

  8. Is there publically available information, such as publications or registered clinical trials, from Researchers/Companies/Institutes using the cGMP iPSC MCBs to generate a human therapeutic product?

    The RMP will track publically available publications, patents and clinical trials associated with the cGMP iPSC line and post them (semi-monthly) to the RMP publications webpage. The generation of the cells is described in the following publication:

    Baghbaderani BA, Syama A, Sivapatham R, Pei Y, Mukherjee O, Fellner T, Zeng, Rao MS. Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications. Stem Cell Rev. 2016 Jun 10.
    Baghbaderani BA, Tian X, Neo BH, Burkall A, Dimezzo T, Sierra G, Zeng X, Warren K, Kovarcik DP, Fellner T, Rao MS. cGMP-Manufactured Human Induced Pluripotent Stem Cells Are Available for Pre-clinical and Clinical Applications. Stem Cell Reports. 5:647-659, 2015 Oct 13

  9. What is the role of the Food and Drug Administration (FDA) in using the cGMP iPSCs?

    Researchers/Institutions/Companies wanting to use the cGMP iPSC line in non-human, pre-clinical studies do not have to notify or file any paperwork with the FDA. Researchers/Institutions/Companies wanting to use the cGMP iPSC line in human clinical trials must first submit – and receive approval of – an Investigational New Drug (IND) application with the FDA. The FDA will consider the merits of each IND according to its guidelines and make the final decision whether or not the specific cGMP iPSC line in question can be used in clinical investigations. Additional questions about this process should be directed to the FDA.

  10. What is 21 CFR 1271 and was it followed during the generation of the Master Cell Bank?

    21 CFR 1271 is a Code of Federal Regulations dealing with Human Cells, Tissues, and Cellular and Tissue-Based Products. Yes, informed consent and IRB approval was obtained for generating both the WCB and the MCB. A copy of this document is included with shipments of WCB and MCB.

  11. Has viral testing been conducted on the iPSC WCB and the cGMP iPSC MCB and where can I receive the documentation?

    Viral testing has only been performed on the cGMP iPSC MCB and the results are summarized in the MCB Certificate of Analysis which will be provided to all recipients of the cGMP iPSC MCB (see number 5 above). Please contact QC subject matter experts Allison Hoffman (allison.hoffman@lonza.com) and Michelle Sison (michelle.sison@lonza.com) for any additional questions regarding the viral testing.

  12. Are there any contractual limitations associated with the iPSC WCB or the cGMP iPSC MCB?

    There are no contractual restrictions associated with the iPSC WCB (remember these cells cannot be used in human trials but that is a quality restriction rather than a contractual restriction). There are contractual restrictions associated with the cGMP iPSC MCB prohibiting for-profit entities from using the iPSCs without prior consent from iPS Academia Japan, Inc. The IPSAJ license policy reads:
    • “Non-for-profit entities may use the intellectual properties without payment solely for research and educational purposes, provided that any sort of commercial purposes are not involved. This, however, does not mean a grant of license. Further, it is prohibited to provide for-profit entities with iPS cells or their derivatives without prior written consent of iPS Academia Japan, Inc.”
    • “Basically, licenses to for-profit entities will be non-exclusive with appropriate and reasonable royalties applied. As to non-platform technologies, however, exclusive licenses may exceptionally be granted to for-profit entities as far as they fulfill certain conditions. (Revised as of October 1, 2015)”
    Each Party receiving the MCB should conduct their own due diligence to determine if their actions or products have freedom to operate.

  13. Do any of NIH’s guidelines on human stem cell research apply to the iPSC WCB or the cGMP iPSC MCB?

    Yes, there are two restrictions for scientists who conduct research with NIH funding using the iPSC WCB or the cGMP iPSC MCB. Section IV of the NIH stem cell guidelines state: Research Using hESCs and/or Human Induced Pluripotent Stem Cells That, Although the Cells May Come from Eligible Sources, is Nevertheless Ineligible for NIH Funding.

    This section governs research using hESCs and human induced pluripotent stem cells, i.e., human cells that are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers. Although the cells may come from eligible sources, the following uses of these cells are nevertheless ineligible for NIH funding, as follows:
    • Research in which hESCs (even if derived from embryos donated in accordance with these Guidelines) or human induced pluripotent stem cells are introduced into non-human primate blastocysts.
    • Research involving the breeding of animals where the introduction of hESCs (even if derived from embryos donated in accordance with these Guidelines) or human induced pluripotent stem cells may contribute to the germ line.
    Please see http://stemcells.nih.gov/policy/pages/2009guidelines.aspx for the complete National Institutes of Health Guidelines on Human Stem Cell Research.

    Update from September 23, 2015: NIH released a guide notice slightly modifying the above restrictions; NIH will not fund any new or competing grant applications or contract proposals for research in which human pluripotent cells are introduced into non-human vertebrate animal pre-gastrulation stage embryos.
    Update from August 4, 2016: NIH is considering amending Sections IV and V of the NIH Guidelines for Human Stem Cell Research and published a guide notice requesting public comments by the close of September 6, 2016. Submit comments here.

  14. What is the cost of the iPSC WCB and the cGMP iPSC MCB?

    The iPSC WCB and the cGMP iPSC MCB are priced reflecting a cost recovery model for recouping shipping costs (e.g. cGMP shipping requirements for the cGMP iPSC MCB) and costs to expand the lines. The iPSC WCB will be distributed according to established NHCDR guidelines: $500 per vial for non-profit investigators and $1,500 per vial for commercial recipients. The cGMP iPSC MCB will be distributed at a slightly higher cost reflecting the additional cGMP conditions these cells are required to be maintained under: $1,000 per vial for non-profit investigators and $5,000 per vial for commercial recipients. Sharing of the cGMP iPSC MCB is not be permitted.

This page last reviewed on November 30, 2016