"Integration of Taoism and Devices" Helps China Biopharmaceuticals

With decades of accumulation, under the active guidance of the government and the joint efforts of all practitioners, biomedicine has now become one of the hottest fields in the pharmaceutical industry, showing a thriving trend

However, there are hidden worries under the prosperity

Therefore, except for a few completely innovative products, most antibody or protein drugs will fall into fierce competition

How to stand out in the fierce competition in the future and continue to provide efficient and accessible biological drug therapy for unmet clinical needs will be a problem that relevant companies have to think about

Mainly the production cost

Therefore, if the test of biomedicine in the first half is the speed of research and development, then the magic weapon for winning in the second half may be the production capacity

In the field of antibody or protein products that rely on cell culture, there are two main directions for the exploration of increasing production capacity

One direction is to increase the expression per unit volume through process intensification, and finally embark on the path of continuous production through upstream perfusion and downstream continuous chromatography

At present, there are enterprises conducting research in both directions, and the future development direction is likely to be the integration of the two directions, and eventually large-scale continuous production will be realized

At present, in terms of regulatory constraints and technical feasibility, it seems relatively easy to increase the volume of a single tank, and many companies have already begun to make arrangements

This paper will also elaborate in this direction

Unfortunately, at present, domestic bioreactor manufacturers rarely have the experience and cases of reactor manufacturing with a volume of more than 10KL, and the manufacturing cases of foreign suppliers are also very limited

So what are the difficulties in designing and manufacturing large-scale bioreactors for cell culture?

The answer is "process suitability", not tanks, piping, instrumentation, valves and control systems

At present, the industry still has a very limited understanding of the cell culture process, and the regulation strategy is relatively lacking.

But as the reactor volume expands, the performance of heat transfer, mass transfer, momentum transfer, and reaction engineering can change dramatically, and this change can cause our existing processes to fail or not achieve the desired results, in short The reactor "doesn't fit" with our usual process

How to improve the continuous process "fitness" of the reactor during scale-up? There have been many literatures discussing some basic principles that should be followed in the amplification process from a technological point of view, and will not be listed here

From a large-scale reactor development perspective, several test points are usually important.
These are energy input per unit volume, superficial gas velocity, oxygen mass transfer coefficient, mixing time, carbon dioxide removal rate, and gas hold-up volume
.

Reflected in the design of the reactor, the first is the height-diameter ratio (H/D).
For reactors below 5KL, the height-diameter ratio is usually between 1.
5-2
.
For reactors above the 10KL liter scale, the literature suggests that a larger aspect ratio close to 3 may be more appropriate
.

And more than 2 mixers will be selected, and the stirring form is no longer limited to the traditional marine type
.
In the design of gas distributors, two or more distributors with both macrobubble and microbubbles may better meet the mass transfer requirements of oxygen and carbon dioxide
.

The above is only a brief example.
It must be admitted that the design and development of large and ultra-large bioreactors is a complex system engineering that requires the cooperation of multiple disciplines such as technology, engineering, machinery, and automatic control
.
As the title of the article says, only "the unity of the Tao and the device" can "carry the Tao with the device"
.

Fortunately, the relevant government departments have also realized that our country is insufficient in the design and manufacture of large-scale bioreactors and cell culture.
>=10,000 liters/tank) cell culture technology”
.

At present, domestic suppliers have also carried out related explorations
.
It is believed that with the joint efforts of everyone, in the near future, domestic large-scale bioreactor design and cell culture technology will usher in new breakthroughs
.

At that time, it will not only benefit biopharmaceutical companies, but also countless patients with clinical needs
.
It is also the original intention and mission of the pharmaceutical people to continue to provide efficient and accessible medicines for the majority of patients
.