FAQ - Clinical iPSCs

A. Donor Recruitment & Tissue Acquisition Process

1. Can REPROCELL provide donor material for your clinical stem cell service?

REPROCELL can efficiently recruit your desired donors and isolate fibroblasts from skin punch biopsies, following guidelines for FDA 21 CFR 1271, EMA COMMISSION DIRECTIVE 2006/17/EC, and PMDA MHLW Notification No.375, including an IRB (Institutional Review Board)-approved informed consent form.

Pathogen testing is performed at CLIA- and EMA-certified laboratories, ensuring compliance with rigorous quality standards. It is conducted using FDA-approved donor screening kits under CLIA (FDA 42 CFR Part 493), and CE-marked testing kits. We follow guidelines for USP29 <1043> Ancillary Materials for Cell, Gene, and Tissue-Engineered Products and EMA COMMISSION DIRECTIVE 2004/23/EC and PMDA MHLW Notification No.375 for raw materials.

All SOPs and documentation follow FDA, EMA, and PMDA requirements for tissue collection for HCTPs (Human Cellular Tissue Product) use.

2. What mechanisms were put in place for the protection of donor privacy and confidentiality?

Donors are de-identified and after tissue collection, are referenced by a unique ID. The donor-ID link is maintained only at the collection site. The consent form and all documents containing the donor identifiers are kept at the collection site in accordance with IRB guidelines.

3. Regarding donor tissue material, is there evidence of free and voluntary informed consent, in conjunction with independent review and oversight, with particular attention given to disclosure of potential research, clinical and commercial applications?

All donors are consented, provided a HIPAA authorization agreement and the Subject Bill of Rights for Clinical collection. The IRB provides an independent review of the documents and practices governing our tissue collection protocols. The donor tissues are fully consented for commercial and clinical use.

B. Starting Primary Cell Types

1. For clinical iPSC projects, what cell types does REPROCELL use as a primary cell source for reprogramming?

Currently, we provide reprogramming services for clinical iPSC projects using fibroblasts from skin punch biopsies as the primary cell source.

2. Can REPROCELL generate clinical iPSCs from fibroblasts provided by the client?

REPROCELL can use sponsor's fibroblasts for reprogramming into clinical iPSCs, provided the cells conform to REPROCELL’s donor collection standards. Upon arrival at our facility, all provided fibroblast lines must include proper documentation and undergo testing for mycoplasma, sterility, and the standard human viral panel.

C. StemRNA™ Clinical iPSC Generation & QC

1. What method of iPSC generation is used?

We use our newest proprietary, integration-free, virus-free StemRNA™ 5.0 Clinical Reprogramming Technology for our clinical-grade stem cell projects.

2. What are REPROCELL’s standard procedural steps in generating clinical iPSCs?

Our clinical manufacturing process consists of certain key steps.

In the first step, a primary fibroblast culture is derived and characterized from a skin punch biopsy.
In the second step, using our proprietary mRNA technology, we generate clinically compatible StemRNA Clonal iPSC Seed Stock lines. These clinical-grade iPSCs are manufactured at state-of-the-art facilities in the USA and Japan. Both sites operate under stringent quality standards, with our ISO 9001:2015-certified laboratory in the US and the PMDA (MHLW)-certified GMP facility in Japan, adhering to highly regulated SOPs guaranteeing exceptional reliability and regulatory alignment.
Additionally, we create research-use only StemRNA Clinical iPSC Pilot Clones corresponding to the Clinical iPSC Seed Clones. These Pilot Clones are ideal for initial proof of concept or scale-up studies (refer to E5).
A Drug Master File (DMF) is filed with the FDA, covering donor screening, fibroblasts clinical collection, and Clinical iPSC Seed Stock generation at our US manufacturing site. The DMF is accessible via a Letter of Authorization (LOA).

3. What standard assays will REPROCELL perform to identify unwanted mutations in the established clonal lines?

Karyotype analysis
WGS
Oncopanel analysis

4. What Quality Assurance (QA) assays does REPROCELL perform on the clinical-grade iPSC lines?

Our Quality Assurance includes, but can be extended:

Morphology check
Viability
Growth rate
HLA and KIR genotyping
Mycoplasma and sterility testing
Endotoxin testing
Pluripotency marker expression (quantitative by immunocytochemistry)
Purity analysis (qualitative by flow cytometry of key markers)
Potency Capability (Trilineage differentiation)

5. What kind of genomic characterization is available for the generated cell lines?

For the primary fibroblast lines, Clinical Seed Stock, and GMP MCB iPSC clones, we perform the standard, low-resolution assays G-band karyology. For higher resolution analysis, we perform WGS and Oncopanel analysis on the donor starting material and the corresponding Clinical iPSC Seed Clones. Please contact us for more information.

REPROCELL can also provide WES, RT-PCR, and Bioinformatics.

6. Can I evaluate multiple Seed Stock iPSC Clones before deciding which one to expand?

We offer you an evaluation period on multiple Seed Stock iPSC Clones to validate your differentiation protocol, perform a proof-of-concept study, and narrow down your clone of interest before expansion into a GMP Master Cell Bank (MCB) process.

D. GMP iPSC MCB Manufacturing

1. What are REPROCELL’s standard procedural steps in generating GMP iPSC MCBs?

Our clinical projects consist of certain key milestones

Upon successful completion of the evaluation period by the sponsor, the chosen Seed iPSC Clone/s can be expanded into a GMP MCB. To meet the more rigorous EMA guidelines, we manufacture MCBs in compliance with FDA cGMP (21 CFR 120, 211), EMA GMP (Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products), and PMDA GMP/GCTP (Good Gene, Cellular, and Tissue-based Products Manufacturing Practice).
Due to the evaluation phase, you can use the same iPSC clone starting from preclinical work, up to the clinical and commercialization phase.

2. What kind of characterization and safety test results are available for the generated cell lines? Which release assays are used to validate GMP MCBs and WCBs?

REPROCELL manufactures GMP MCBs at two sites, in Europe and the US. All GMP release assays are performed in accordance with ICH Q5A/D guidelines. Methodology and assays follow FDA, EMA, and PMDA guidelines. Please contact us for more information.

3. What is the ISO classification of the GMP suites?

The GMP manufacturing suites meet ISO-5 and ISO-7 guidelines.

E. Pricing & Royalties

1. Are there any royalty payments or other fees?

There is a one-time royalty fee per iPSC clone payable to REPROCELL at the time of purchase of the StemRNA Clinical Seed iPSC clones after successful evaluation. Once this fee is paid, the ownership, documentation, and all commercial and therapeutic rights are transferred to you. Unlike royalty schemes for other iPSC technologies, there are no other milestone payments or running royalties.

2. What licenses do I need?

REPROCELL’s proprietary StemRNA™ Clinical Reprogramming Technology will enable you to use the cell lines without acquiring other licenses regarding the iPSC generation technology, with the exception of relevant and corresponding license programs established by iPS Academia Japan, Inc. (Subject to your own legal due diligence).