Frequently Asked Questions (FAQ)
- How do I place an order?
All orders must be placed through the online catalog.The catalog is searchable by disease, genetic disorder, etc. and cell lines can be selected and placed into a cart for checkout.The cart also contains a button to upload a signed copy of the appropriate MTA which can be found on the “Documents” tab of the website.An MTA must be attached in for the order to be placed.
A wiki describing the ordering process can be found at https://saclab.atlassian.net/wiki/spaces/NSRDOC/pages/36864011/How+to+Order+Lines
- How can I get a quote?
Once you have transmitted your order, our business group will send a price quote for your approval, with instructions on how your order will be fulfilled.
- Can I get a quote without placing an order?
Unfortunately, the only way for you to get a quote is through placing an order online through the NINDS catalog.The orders are non-binding and can be canceled if you decide not to move forward with the order.
- How much do the cells cost and what is the shipping cost?
The NHCDR, per NINDS directive, operates on a cost recovery basis and therefore is required to charge academic investigators $500 per vial plus shipping for iPSCs and $325 per vial plus shipping for fibroblasts (FCLs).
Costs for commercial entities are $500 per vial plus shipping for FCLs and iPSC are $1500 per vial plus shipping.
GMP grade cell lines are available to academic investigators for $1000 per vial plus shipping and $5000 per vial plus shipping for commercial clients.
Once an order is placed, you will receive a quote that contains the cell line cost and the estimated shipping fee.Once we receive a PO or other form of payment, we will process your order.After the order ships, we will send an invoice that contains the cell line cost as well as the actual shipping charges.
- Once I place an order how long does it take to get my cells?
Once an order is placed, you will receive a quote that contains the cell line cost and the estimated shipping fee.Once we receive a PO or other form of payment, we will process your order.iPSCs and any international shipments are shipped in a cryoshipper, therefore there is a 4 week shipping queue as the cryoshippers have to be returned before more orders can be shipped out.
For fibroblast shipments domestically, the shipping queue could be between 2-4 weeks depending how many orders are ahead of you.
- What is QC? What is the difference between QC and QC+?
All iPSC cell lines produced by IBX have been subjected to a basic quality control (QC) package which includes testing for sterility, mycoplasma, viability, identity, expression of alkaline phosphatase and FACS for markers of stemness.Clones marked as QC+ have undergone the most extensive QC package, which means that in addition to basic QC tests, the clone was also tested for karyotype, loss of reprogramming factors, differentiation into all 3 germ layers and a more in-depth large-scale gene expression assay to verify stemness.
- Where can I find the Certificate of Assurance?
You can find the Certificate of Assurance (COA) for each of the cell lines in the catalog under the information for each cell line.In addition, when your cells are shipped, you will also get an email with all the information needed for your order including the applicable COAs.
All iPSC and FCL generated at IBX have COAs.Fibroblast cell lines generated before the NHCDR was hosted at IBX do not have COAs.
- Why can’t I find any information on my cells? Where is the COA for the cells I ordered?
The existing NINDS fibroblast and iPSC collection was transferred to IBX from Coriell in late 2015.At that time, all NINDS fibroblasts and iPSCs that were being distributed by Coriell were sent to us and NINDS made a programmatic decision to have IBX distribute the previously existing cell lines as is.This means that IBX has not thawed or otherwise done QC on the cell lines produced by Coriell.
Unfortunately, Coriell did not produce a Certificate of Assurance for the fibroblast cell lines they made which means all we have are the density of the cells initially frozen in each vial.You will be able to find this quantity in column O of the manifest that you will receive when your cells ship.
For iPSCs, Coriell produced a Certificate of Assurance for the cell lines they made which you will receive with your shipment.This document will contain some recommended culturing information from Coriell.
- Do you provide guidelines for culturing iPSCs?
When your cells are shipped you will get an email with all the necessary information including COAs, passage information and guidelines for thawing and culturing your cells. This is also in the documents section of the website and can be downloaded here.
- Where can I find the MTA?
Cell lines in the NHCDR fall into 4 different groups with 4 different MTAs.The MTAs can be found under the “Documents” tab in the catalog application. Please be sure to upload the completed MTA as prompted via the website when placing an order through our online catalog.
The 4 MTAs are as follows:
- The general NINDS lines with their NINDS MTA
- Target ALS lines with their MTA
- The research grade iPSC line with its own MTA
- The GMP iPSC line with its own MTA
11. Do I need to submit an MTA for every cell line I order?
If you have a completed MTA and want to place another order for a line in the same collection, you can use the same MTA, but it needs to be uploaded again.If you want to order a line from a different collection, a new MTA needs to be completed.
- Can I request changes to the MTA?
The language in the existing MTA was approved by both NIH and the IBX legal office and NINDS feels strongly that all recipients of the NINDS cell lines need to have the same MTA as this alleviates the need to track the language used in different MTAs. At this time NINDs is not considering any language changes unless there are extremely extenuating circumstances.
- What happens if am reaching the 5-year mark and my MTA is expiring for the cell line I ordered?
At the 5-year time point, all you have to do is send us a new signed MTA and we will add it to your order information
- What information is needed in the statement of research interest?
The statement of research interest (SRI) does not need to be in a specific format. A simple paragraph about your planned usage of the cell lines is all that is necessary. NINDS asks that you not submit any proprietary information in your SRI.
GMP iPSC Cell Line FAQ
- How do I order GMP iPSCs?
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. Therefore, 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-IND meeting with the FDA or a letter of Cross-reference for the drug master file as part of the ordering process. Once you have that, the order process is similar to any other cell lines you order from our catalog. Refer to FAQ #1 for help with the order procedure.
- What is the cost of the iPSC working cell bank (WCB) and the cGMP iPSC master cell bank (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.
- 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 (Word document) provided by Lonza, also provided by Lonza.
- How can I get a letter of Cross Reference for the Drug Master File (DMF) for the GMP iPSC cell line?
A letter of cross reference for the DMF can be obtained by contacting Lonza using the request letter template.
- 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 a current Good Manufacturing Practices (cGMP). The iPSC WCB (also generated by Lonza Walkersville) is from the MCB. After the MCB was derived and certified as cGMP, a vial of MCB was expanded under non-cGMP condition 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 generation of the cells is described in the following publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919381/. See also: cGMP-Manufactured Human Induced Pluripotent Stem Cells Are Available for Pre-clinical and Clinical Applications. Baghbaderani BA, Tian X, Neo BH, Burkall A, Dimezzo T, Sierra G, Zeng X, Warren K, Kovarcik DP, Fellner T, Rao MS, Stem Cell Reports 2015 Oct 13; 5(4):647-59 (PubMed).
- How many cells are in each cGMP vial?
One vial of cells contains approximately 1X106 cells
- 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 Assurance
- Tissue sourcing document with copy of IRB approval (covers MCB & WCB)
- Material Transfer Agreement for WCB
- Instructions for culturing
Documents included with the MCB
- Official Certificate of Assurance
- Tissue sourcing document with copy of IRB approval (covers MCB & WCB)
- Material Transfer Agreement for MCB
- End-user agreements document (covers MCB only)*
- 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 MCB cells from the NHCDR.
- 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: http://ips-cell.net/e/), 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.
- Is there publicly 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 publicly available publications, patents, and clinical trials associated with the cGMP iPSC line and post them (semi-monthly) to the RMP publications webpage. Link provide here: https://commonfund.nih.gov/publications?pid=22.
The generation of the cells is described in the following publication : 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 (http://www.ncbi.nlm.nih.gov/pubmed/26411904)
- What is the role of the Food and Drug Administration (FDA) in using the cGMP iPSCs?
Researchers, Institutions, and 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, and 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.
- What is 21 CFR 1271 and was it followed during the generation of the Master Cell Bank?
Of the six subparts of 1271 (A – F) that apply to use of human cells and tissues in regenerative medicine, subpart B-Registration and Listing, subpart C-Donor Eligibility, and subpart D-Current Good Tissue Practice, were followed to register and list, screen and test donors to determine Donor Eligibility, and to recover tissue (umbilical cord blood) that was used as the starting material to isolate CD34+ cells to generate the Master Cell Bank. Lonza Walkersville, Inc. has responsibility for ensuring that 21 CFR 1271 requirements were followed during the manufacturing process.
- 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 Assurance which will be provided to all recipients of the cGMP iPSC MCB (see number 5 FAQ above). Please contact QC subject matter experts Allison Hoffman (email@example.com) and Michelle Sison (firstname.lastname@example.org) at Lonza for any additional questions regarding the viral testing.
- Are there any contractual limitations associated with the iPSC cGMP iPSC MCB?
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 can be found at http://ips-cell.net/e/license/policy.html.
Each Party receiving the MCB should conduct their own due diligence to determine if their actions or products have freedom to operate.
- 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 human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs), 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 iPSCs 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 iPSCs 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.