US-based company Allele Biotechnology & Pharmaceuticals has received a tissue bank licence from the California Department of Public Health. Headquartered in San Diego, the biotech firm said this makes it the world’s first establishment to collect tissue for the manufacture and banking of induced pluripotent stem cells (iPSCs) for commercial applications.
Allele’s cGMP facility is dedicated to the generation, banking, and differentiation of iPSCs for therapeutic use and drug discovery.
All tissues and cells are processed in a state-of-the-art cleanroom to satisfy FDA requirements for Phase III clinical trials and commercial production. The cleanroom’s modular space and adaptable design allow different areas to be dedicated to the manufacture of various iPSC-derived cells.
Speaking to Cleanroom Technology, an Allele spokesperson explained: "To our knowledge, no fully cGMP-compliant cell line has been generated where the entire manufacturing process, from tissue sourcing to cell expansion and banking processes as well as documentation, raw materials, staff training, cell therapy facility, and quality control (QC) testing, has been validated.
"Stem cell-based therapies are going to be different than other products because the continuity of the cells to be used in both early phases of the trials and phase III and commercial production; therefore, Allele promotes the concept of going full cGMP from the beginning, and proved such a path that wasn’t available previously.
The Allele spokesperson pointed out that groups that used to use R&D cell lines and tried to qualify them for early trials should plan differently now. "Each process is key to being most compliant with FDA guidelines and thus the most clinically compatible. To avoid contamination during tissue recovery and to diminish the risk of introducing, transmitting, or spreading a communicable disease through the use of a HCT/P, the quality program addresses core cGTP requirements. Reagents, equipment and all materials are compliant with cGMP standards and regulations. Our protocol is designed to ensure fibroblasts are healthy and cultured under optimal conditions for successful reprogramming. And, our process was developed to achieve consistent results across individual donor lines."
Novel manufacturing
The first tissues were processed in August 2017 when the cGMP manufacturing suite officially opened after a 2-year construction and remodeling effort and nearly a decade of iPSC reprogramming research and optimisation.
The iPSCs generation process is fully cGMP- and GTP-compliant, beginning with the onsite collection of tissue from donors or clients by a physician.
All cGMP manufacturing personnel have undergone extensive training with strict qualification and documentation measures to ensure successful reprogramming of cells in an ISO-5 environment.
Once generated, iPSCs are banked and can be distributed or differentiated for transplantation into patients. The entire process is validated and performed under the umbrella of a 21 CFR-compliant quality system.
Generation of iPSCs is based on Allele’s proprietary mRNA-only protocol that was designed and optimised expressly for cGMP production. The methods were developed to produce iPSCs that are free from genomic integration of plasmid DNA, viruses, and feeder cells.
“The powerful mRNA technology developed by Allele’s researchers made it much easier for cells to enter clinical trials down the road and we expect multiple patent issuances shortly,” explained Dr. Jiwu Wang, CEO and lead scientist behind the technology.
The facility has a dedicated mRNA production area for the manufacture of cGMP-compliant mRNAs. In addition to supporting ongoing iPSC reprogramming efforts, cGMP mRNA will facilitate ongoing internal development programs to generate iPSC derived cells.
Current efforts are focused on the production of pancreatic beta cells, neurons, oligodendrocytes and their progenitor cells, hepatocytes, muscle cells, and mesenchymal cells.
Established in 1999, Allele Biotechnology’s mission is to further therapeutic innovation and support clinical studies by providing cutting edge technologies and clinical-grade solutions to partners in the stem cell therapy arena.