Improving the quality of regenerative medicine

High-precision quality control and manufacturing of cells for medical use

Introduction

Regenerative medicine taking steps forward

Curing illness with living cells: a dream medicine

With the capacity to cure currently incurable illnesses, regenerative medicine holds extraordinary potential for people suffering from illness and injury for which there has been no hope. A dream medicine, regenerative medicine can bring great happiness to patients and those around them.

By transplanting living cells, regenerative medicine can regenerate organs and tissues that have lost their function through illness or injury and restore them to their original state. The potential applications for regenerative medicine are vast and include treatments for intractable diseases; sequelae after unforeseen recovery from cerebral infarction or spinal cord injury; chronic illnesses such as diabetes mellitus for which ongoing treatment imposes tremendous physical, time, and financial burdens; and disorders requiring organ transplant. Thus, regenerative medicine offers an answer to many currently unmet medical needs.

The current medical approach to treating organs and tissues that have lost their function primarily involves small-molecule drugs and medical devices. Unfortunately, despite their effectiveness as a supportive measure in eliminating pain and discomfort and slowing disease progression, small-molecule drugs do not always offer a complete cure. Similarly, while cardiac pacemakers, prosthetic joints, and artificial dialysis can compensate for lost physical function, they often require repeat surgery for maintenance or frequent regular therapy, placing large physical and mental burdens on the patient. Meanwhile, although organ transplant presents one of the few curative approaches, the lack of suitable donors means each patient’s chance of surgery is low.

Today’s medicine is built on progress made during the long history of humankind. Unmet medical needs still exist and the world is waiting for regenerative medicine to satisfy these needs. The goal of regenerative medicine is a world that gives all patients the chance to receive a complete cure.

An all-out national commitment

Expectations surrounding regenerative medicine are extremely high. In Japan, enhanced industry, academia, and government collaboration are moving the dream toward reality. An industry group comprising more than 250 participating companies, the Forum for Innovative Regenerative Medicine (FIRM), is at the center of industrial efforts to promote the widespread use of regenerative medicine, build a business ecosystem for industrialization, and become internationally competitive. Academic bodies in Japan, particularly the Japan Society for Regenerative Medicine, are leading the world in regenerative medicine research and driving forward trials to translate the results of research into clinical application. Politically, the Japan Agency for Medical Research and Development (AMED) has an enormous annual R&D budget of 15 billion yen to spend in the field and recent regulatory developments support prompt, safe treatment using regenerative medicine for the Japanese people. In Japan, major legislative measures include the Regenerative Medicine Promotion Act and the Therapeutic Products Act (the revised Pharmaceutical Affairs Act) enacted in 2014. A rapid explosion in the potential market value of regenerative medicine is expected with current estimates of 12 and 38 trillion yen globally and 1 and 2.5 trillion yen domestically, for 2030 and 2050, respectively.

Backed by TEAM JAPAN, comprising members from throughout industry, academia, and government, there is an all-out national commitment to realizing the potential of regenerative medicine to satisfy patients’ unmet medical needs.

Issue

Major issues facing regenerative medicine

The cell-based products used in regenerative medicine are composed of living cells. This enables unique treatment results not possible with conventional drugs composed of small-molecule compounds. However, it also presents handling difficulties. In order to manufacture cell-based products, cells must be cultured. Culturing is the process by which cells are cultivated in the specific growth environment required by that cell type until the number of cells necessary for the particular product is reached. Living cells are incredibly complex systems that can alter their characteristics in response to changes in the culture conditions. Since cell-based products contain large numbers of living cells that are sensitive to the culture environment such as the culture conditions (including the culture medium and scaffold), techniques, and process, they are prone to variability. Variability in cell-based drug products must be tightly controlled.

How to overcome cell variability, which impacts the quality of cell-based products, is a major issue for regenerative medicine.

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Solution

Two technologies for controlling cell variability

Solution 1: High-precision cell quality control

One solution is to increase the precision of cell quality control.

Increasing the precision of quality and in-process control testing allows cells to be assessed regarding whether they have been correctly manufactured, enabling the shipment of only high quality cell-based products. However, it is said that the quality testing cells to determine whether they have been correctly manufactured is quite difficult.

Our cell measurement technology uses high-precision, single-cell transcriptome (the comprehensive gene expression profile) analysis together with machine learning. This technology was developed by RIKEN and AMED as part of the government-backed Japan Regenerative Medicine Project (Press release), of which one of our founders was a central member. Using this technology, it is possible to accurately analyze and determine the cellular composition of target cell populations, such as those in cell-based products, and the kind of indicator genes that characterize the state of cells. This information enables the establishment of high-precision quality control testing and the shipment of only high quality cell-based products. The overall result is stable production and shipping systems with low variability, which also contributes to reducing excess costs.

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Solution 2: High-precision cell manufacturing

The second method for resolving variability in cell-based products is to fundamentally reduce the variability arising during manufacturing. As described above, by establishing indicators for high-precision evaluation of cell manufacturing, it is possible to increase productivity of cells.

Our cell cultivation technology uses high-throughput screening of cell culture conditions. Solution chemistry and robotic technology are used to produce many different culture conditions while comprehensive gene expression profiling and machine learning are used to search for the precise culture conditions that will encourage proliferation of the target cells in a more active state. The indicator genes identified using the cell measurement technology described above play an important role in selecting the appropriate conditions. Using existing methods, cells lose their functional activity and proliferative ability through repeated successive culture. However, by culturing under the culture conditions created, it became possible to grow more cells, for longer, and with greater stability.

As a result, the amount of variability decreases and it is possible to manufacture cells with little difference between lots. Reduction of rejected lots and significant improvements in yield also help to cut manufacturing costs. As of 2019, development of this technology was moving toward completion.

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Target result

We believe that the two solutions described above can answer the major issue of how to overcome cell variability, which impacts the quality of cell-based products in regenerative medicine. The quality control and manufacturing system able to tightly control cell variability resulting from increased precision of quality control and manufacturing of cells for medical use increases the overall quality of regenerative medicine.

At Knowledge Palette, Inc., we collaborate with pharmaceutical companies and venture companies that are driving improvements in the quality of regenerative medicine as well as research organizations such as universities that are working on the practical application of regenerative medicine.

Please Contact us for further information regarding our work on improving the quality of regenerative medicine.

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