StemCells, Inc. - Tools & Technologies: Manufacturing

Manufacturing

StemCells has pioneered innovative manufacturing methodologies in order to supply our therapeutic clinical development programs with HuCNS-SC^® human neural stem cells. For clinical trials, the HuCNS-SC product candidate is manufactured according to current Good Manufacturing Practices (cGMP), in a US Food and Drug Administration (FDA) registered facility. Expandable and bankable, HuCNS-SC cells can ultimately be “manufactured” at commercial-scale as “stem cells in a bottle,” then distributed for patient doses, much like an off-the-shelf pharmaceutical product.

Manufacturing of HuCNS-SC Cells

We have manufactured our HuCNS-SC product candidate for clinical trials since 2006. Manufacturing is performed in a cGMP-compliant facility, by highly qualified personnel working in a clean room production environment. Our Quality System approach is designed to ensure that controls are implemented and completed satisfactorily during manufacturing operations, and that developed procedures and specifications are appropriate and followed, including those performed by contract testing laboratories.

Our HuCNS-SC cell banks are purified and expanded in culture prior to cryopreservation. These cell banks remain stable for many years and are used for the onward production of our final product — the HuCNS-SC cells that will be transplanted into patients.

Stewart Craig, PhD
Senior Vice President, Development & Operations

“It’s no mean feat converting great science into commercial reality. At StemCells, we've got a world class team tackling it.

Researchers have been studying stem cells in the laboratory for as long as the biotechnology industry has been in existence. I've been involved in biotech since the early 80s, when I began working on development, characterization and manufacture of recombinant biopharmaceuticals. For the past 16 years, my focus has been on stem cells and other cell-based therapies, which promise to be the next wave in medicine.

The challenge is how do we realize that promise within an evolving regulatory framework? Cell-based therapies present some unique considerations in terms of regulatory strategy, process development, product characterization, manufacturing and distribution. However, combining sound basics with the simple heuristic application of our experience allows us to creatively address these elements in order to ultimately deliver and administer stem cell therapeutics at commercial scale and cost.

In the end, it’s just like playing rugby: You win when you have an experienced group of players who work as a team and are situationally aware of where the ball is at all times — and of where the next punch may be coming from!”

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“It’s no mean feat converting great science into commercial reality. At StemCells, we've got a world class team tackling it.

Researchers have been studying stem cells in the laboratory for as long as the biotechnology industry has been in existence. Read the full story…

Stewart Craig, PhD
Senior Vice President, Development & Operations

Our Manufacturing Process

HuCNS-SC cells are manufactured through a multi-step process consisting of four stages:

Cell Sorting
Cell Culturing
Cell Banking
Final Product

Cell Sorting

The first production step comprises a proprietary method for purification of HuCNS-SC cells from donated fetal brain tissue procured from an FDA-registered, not-for-profit agency, in compliance with Good Tissue Practice (GTP) and all other applicable state and federal regulations. As part of the purification process, cells from the tissue are “tagged” with a monoclonal antibody that recognizes human neural stem cells. High-speed Fluorescence Activated Cell Sorting (FACS) is then used to isolate the cells tagged by the monoclonal antibody. The FACS-isolated HuCNS-SC cells are then placed in cell culture.

Cell Culturing

Further purification of the FACS-isolated HuCNS-SC cells is achieved through selective cell culture in a defined, serum-free medium. From one tissue source, we are able to grow billions of cells, which can be used to create cryopreserved cell banks. Extensive testing has shown that the HuCNS-SC cells retain their in vitro and in vivo potential for multi-lineage differentiation to form all three types of central nervous system (CNS) cells — neurons, astrocytes and oligodendrocytes — throughout extended cell culture.

Cell Banking

HuCNS-SC Master Cell Banks (MCBs) are cyropreserved at an early cell culture stage, and are the source of HuCNS-SC Working Cell Banks (WCBs), which are cryopreserved at later cell culture stages. In compliance with US and International regulatory guidelines, MCBs and WCBs are extensively tested and must meet quality control specifications for attributes of safety, purity, identity and potency in order to be released for use in onward manufacturing. Similar to traditional biotechnology cell culture production, multiple WCBs can be created from a single MCB and many final product doses can be created from each WCB.

Final Product: “Stem Cells in a Bottle”

HuCNS-SC patient doses are manufactured from a Working Cell Bank (WCB). For release, the final product must once again meet a series of quality control specifications for safety, purity, identity and potency. When test results indicate that the specifications have been met, Quality Assurance releases the final product for distribution and clinical use. Our “stem cells in a bottle” are supplied in sterile vials, as an aseptic suspension of cells for surgical transplantation.