How does Merck do well in China's pharmaceutical process behind the production of Taibang biological blood products...

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Merck-Tabon Biotech Signing Ceremony

At the 60th (Spring 2021) National Pharmaceutical Machinery Expo and China International Pharmaceutical Machinery Expo, Merck, the world’s leading provider of technological process solutions, and my country’s leading blood product company-Shandong Taibang Biological Products Co.

Wang Bin, Director of China Technology and Service Solutions, Merck Life Science Process Solutions

According to Mr.

It is worth noting that in addition to the production process solutions of Taibang Bio-Blood Products, Merck has been playing an increasingly important role in the innovation and development of China's biomedicine in the decades since entering the Chinese market.

01 Hand in hand with Taibang to overcome difficulties in blood product process development and amplification

As we all know, the biopharmaceutical industry has many barriers, and the blood products industry is full of barriers.

Suga Nagayoshi, Director of R&D and R&D Center of Taibang Biological Group Co.

In this regard, Suga Nagasaki believes that expanding the production scale of blood products and upgrading the variety structure has become the key to directly determining the future prospects and fate of blood products companies.

"However, due to the scarcity of raw materials for blood products and the risk control in the production process, during the process of capacity expansion, the defects of the traditional production process have been exposed, because this is not a production process that can be easily replicated and amplified.

Suga Nagasaki said that Taibang Biosciences chose to deepen cooperation with Merck, first of all based on the trust of the long-term cooperation between the two parties.

The second is based on Merck's global vision and its technical and talent advantages in China.

It is reported that this time Merck will use its downstream separation and purification technology capabilities and process model analysis capabilities to help Taibang Biology develop a new generation of blood product production processes.

In this regard, Merck Wang Bin further elaborated: “Traditional plasma purification is based on the low-temperature alcohol precipitation process and has a history of decades.

In addition, both parties have expressed great expectations for the future cooperation.

Suga Nagasaki stated that Merck, as an upstream supplier of pharmaceutical companies with an international perspective, hopes to continue to select and bring more and more advanced technology and service options to the global market in the future.

02 Plow China in depth: innovation-driven solution to difficult problems

Not only in the field of blood products, looking at the development of my country’s biomedical industry, most pharmaceutical companies tend to regard sales as the king at the beginning.

In recent years, a series of medical reform policies have been promulgated, such as the new version of "Drug Management Law", "Vaccine Management Law", consistency evaluation of generic drugs, "4+7" volume procurement, guidelines for preclinical research related to biological products, and my country's accession to ICH The later changes in the policy environment have had a profound impact on the competition pattern and industrial ecology of the entire pharmaceutical industry, making Chinese pharmaceutical companies have to go back to the source to face the problems of "quality" and "cost".

As a result, under the trend of policy guidance and market competition, the focus of enterprises on the "quality" and "cost" of drugs has gradually moved forward.
The use of innovative techniques to improve production efficiency and reduce production costs has begun to become an enterprise in the fierce competition.
Based on the foundation, the concept of "Quality comes from design" (QbD) has also been deeply rooted in the hearts of the people.

"Quality comes from design" (QbD)

Based on the pre-set Target Product Quality Profile (TPQP) as the starting point for research and development, based on understanding the Critical Material Attribute (CMA), through Design of Experiments (DOE), Understand the critical quality attributes (Critical Quality Attribute, CQA) of the product, establish the critical process parameters (Critical Process Parameter, CPP), and establish a robust process that can meet product performance under multiple influencing factors such as raw material characteristics, process conditions, and environment According to the design space, establish quality risk management, establish quality control strategy and product quality system (Product Quality System, PQS), and emphasize the understanding of products and production throughout the process.
QbD includes product design and process design before the market, as well as process implementation after the market.

In Wang Bin's view, the concept of "Quality by Design" (QbD) is that process development needs to be considered from the beginning, the so-called end is the product itself.
He believes: "With the large-scale industrialization of China's biopharmaceutical industry, how can laboratory research and development results be successfully scaled up to commercial production scale? The challenge of process scale-up is that the amplification of many parameters is often not linear.
A challenging topic at the moment.
"

"The pharmaceutical industry is an industry with extremely high regulatory and regulatory requirements.
The pharmaceutical industry has always been a very conservative industry.
It has been slow to accept new technologies and processes, and once the production process is declared and finalized, even if the new process developed later has obvious advantages, It is also very difficult for manufacturers to adopt new processes to replace old processes.
On the one hand, the verification cost of new processes is high and the risks are high.
On the other hand, new processes often need to be reinvested in new equipment.
In particular, process development and production are often different from each other.
The two teams are responsible for the problem.
The focus of the two teams is often very different.
Therefore, the challenge of process scaling is that the scaling of many parameters is often not linear.
How to establish a stable scaling model is very important.
"

Wang Bin introduced that in response to such needs, Merck opened the M Lab™ collaboration center in Zhangjiang, Pudong, Shanghai to provide more advanced process solutions for the Chinese market from many aspects——

• In terms of industrialization: The center provides customized solutions specifically for the field of life sciences in China to help Chinese pharmaceutical companies promote drug development.
  Currently, the center includes 14 laboratories including pilot test and process development laboratories, where biotech companies, pharmaceutical and biopharmaceutical manufacturers, etc.
  can explore ideas, learn innovative technologies, and work side by side with Merck’s scientists and engineers.
  Solve key process development and production challenges.
  Customers can participate in product demonstrations, hands-on training, formal biotechnology education courses and experiments, and use best practices and innovative methods to develop, optimize and expand processes and simplify global technology transfer.
  
• In terms of digitalization: The center has the Merck Bio4C™ digital platform.
  The Bio4C™ platform is part of Merck's BioContinuum™ continuous flow process platform automation and analysis platform, which consists of independent, seamlessly compatible software products.
  The intuitive interface and easy-to-access functions enable a broad user base to collaborate with cross-border global teams, such as timely control, monitoring and analysis of equipment, processes, results and data.
  Based on the core of 4C (Control, Connect, Collect, Collaborate), the Bio4C™ platform provides an integrated and open digital environment to adapt to different production, process and regulatory requirements.
  It provides complete transparency and intelligence, with data-driven as the core to manage the entire process and factory.
  
• In terms of regulations: After entering the Chinese market for many years, Merck has been paying attention to the impact of policies and regulations, and has actively participated in the writing of relevant guidelines for the pharmaceutical industry, including "Guidelines on Sterilization and Filtration Technology and Application", "Therapeutic Biological Products Virus Key Points for Pollution Risk Control, "Compilation of Application Technical Documents of Foreign Pharmaceutical Disposable Systems", etc.
  Nowadays, Merck has established a strong quality and regulatory support team in my country to help Chinese biopharmaceutical companies provide consulting services on the quality and regulation of the entire drug life cycle to meet the increasingly stringent regulatory requirements and international industry standards.
  

03 Looking to the future: Continuous flow process accelerates changes in the era of biopharmaceutical 4.
0

"Curiosity drives us to continue to innovate, let us continue to explore solutions to major scientific and technological problems in the future", Wang Bin emphasized that innovation is the most important "gene" in Merck's blood.

For the most promising new process in the future, Wang Bin's answer is: continuous flow process.

In his view, the production of traditional biopharmaceuticals uses a batch production process, which requires a series of interval production steps.
Every interval in the entire process will bring about a reduction and delay in production efficiency, and increase the probability of product defects and operational errors.

The continuous flow process is an emerging technology.
Although it still faces many challenges, the superiority of continuous production is already obvious-it can not only improve the robustness and reliability of the production process, reduce production and fixed asset expenditures, but also reduce the number of factories.
Construction time, reduce the time required for product replacement in production.

It is reported that the combination of continuous flow process with Internet software, automation and analysis technology to digitally connect all systems and equipment to achieve a complete end-to-end biological process is setting off a biopharmaceutical 4.
0 process revolution.
It is also the direction that Merck's existing BioContinuum™ platform focuses on and actively explores.