The Pharmaceutical Technology Division is in charge of the development process leading to the commercialization of candidate molecules. Within that division, the Process Simulation Group works on the formulation of small and mid-size molecule solid drug products, as well as process design and optimization, using digital technologies. This article explores the significance and rewards of working in drug design at Chugai Pharmaceutical from the perspective of a researcher who joined the company as a mid-career recruit.

(Interviewee: Chikushi)

*Reproduced from Chugai Pharmaceutical’s official Talentbook page (https://www.talent-book.jp/chugai-pharm). Article details and employee positions are current as of July 2024.

Accelerating the development of solid drug products with digital technologies. For the realization of patient-centric formulation development

The Formulation Development Department handles devices, such as injectable drugs, and solid drug products, such as tablets and capsules. One of the characteristics of the Process Simulation Group’s formulation development is the active use of digital technologies in the development of solid drug products.

 

‘Our job is the development of solid drug products, such as tablets and capsules that are administered orally. Actively using digital technologies such as simulation, we examine the formulation development of drug products, forming processes such as powder processing, granulation, tableting, and coating, and the quality assessment of manufactured drug products.

 

While operations are conducted on an experimental basis, in addition to conventional statistical analysis technologies, we actively use various simulation software and AI to improve efficiency, and we work to derive optimal conditions based on less data and fewer examinations.

 

Our mission is to ensure that safe, high-quality products are delivered to patients promptly. For formulation development and optimization with a view to mass production, we also actively use simulations from a quality assurance perspective when scaling up from the lab to commercial production.’

 

Chikushi is in a position of leading junior researchers. She covers a wide range of operations, from experiments and data analysis to directing teams.

 

‘My areas of responsibility are many and varied, including formulation of small and mid-size molecule solid dosage forms, process design, process development for applications for approval of pediatric solid drug products, and construction of simulation models.

 

Currently, my major roles include setting the direction of projects through close collaboration with project managers, making junior researchers aware of project targets in an appropriate manner, and drawing up concrete action plans in consultation with them.’

 

Chikushi is involved in the development of mid-size molecule solid drug products, which is a focus of Chugai Pharmaceutical’s efforts. As a researcher, she finds this work to be some of the most interesting she has ever done.

 

‘In the development of mid-size molecules, which have a larger molecular weight than small molecules, ensuring stability and improving solubility are important. To enhance dissolution (how the ingredients of a drug dissolve after ingestion) and absorption required for internal absorption, drug product development demands a variety of creative approaches. They include formulation design, which combines excipients that improve solubility with active ingredients, and production design to determine the manufacturing process that will determine how the product is to be produced. While it is challenging, it is a highly rewarding and worthwhile job.

 

Also, one of Chugai Pharmaceutical’s unique advantages is that it is able to collaborate with Roche, one of the world’s leading pharmaceutical companies and Chugai Pharmaceutical’s strategic alliance partner. It's very exciting to have many discussions with them about combining digital technologies and establishing new approaches, such as introducing new technology that has a limited track record in Japan.’

 

Chikushi has been driven by her passion for “patient-centricity.” She talks about the value of engaging in drug product research.

 

‘The Formulation Development Department engages in the development of drug products that patients administer themselves. Therefore, we are always conscious of the patients’ viewpoint, and we can pursue research that considers the impact on patients’ daily life, including how easy a drug is to take. This is a distinctive feature of this department. Compared with the initial phase of drug discovery, this job is closer to patients, and the ability to engage in product development from the patients’ viewpoint is my driving force.

 

Seeing drug products whose development I have been involved in actually been launched on the market and gaining a real sense that the effectiveness of those drugs has been demonstrated is the source of my passion and sense of responsibility.’

Path to drug researcher, and a new challenge at Chugai Pharmaceutical

Influenced by her parents who worked for a pharmaceutical company, Chikushi aimed to be a researcher from early childhood. By the time she entered university, she had already envisioned a career in the pharmaceutical industry.

 

‘I enrolled in the pharmacy faculty, where I engaged in research on improving the solubility of poorly soluble drugs.

 

After graduation, I joined a major Japanese pharmaceutical company. As that company has a track record of launching a wide range of products onto the market, its main approach is to develop new products based on existing success stories. While I did some work in the development of injectables, my main work was in solid drug products involved proceeding with commercialization in accordance with established procedures.

 

In my previous job, opportunities to use new digital technologies were limited. While I very occasionally had the chance to encounter simulation technologies, research and development based on conventional methods of statistical analysis were at the center of my duties.’

 

Chikushi later married and moved to Tokyo, where she joined Chugai Pharmaceutical. She recounts her impressions when she first joined the company.

 

‘The work in the lab was mainly based on teamwork, and when I couldn’t come to work due to my child's sudden fever or similar reason, other members would cover for me. It was an extremely flexible workplace in that regard. In addition, employees are encouraged to take paid leave, and a flextime system has been introduced. Just as I had heard from my former colleague, who also joined the company a little before me, I felt that Chugai Pharmaceutical has a comfortable working environment for women.’

 

Chikushi was assigned to her current department soon after joining the company. She has grown as a researcher in the department’s open and flat organizational structure.

 

‘I participated in projects for the development of oral tablets and capsules and served as a kind of liaison between the lab and the production plant. My main job was the optimization of the process of shifting to large-scale production from lab-scale manufacturing. This was an area where I could leverage the experience that I had gained at my previous employer, so I was able to adapt smoothly.

 

A major feature of Chugai Pharmaceutical is the low barriers between departments. Various divisions, including the Formation Development Department, Analytical Development Department, the drug substance research divisions, the manufacturing plants, Regulatory Affairs Department, and Quality Assurance Department, share information and cooperate with each other in product development.

 

This cross-divisional approach is the very reason that we are able to develop the most appropriate products for patients from multifaceted perspectives. I have found this mechanism, in which ideas and proposals from members with various specializations are quickly aggregated, to be highly effective.’

Leadership nurtured by a frontier spirit, career path broadened in a global environment

Chikushi started actively working as an immediate asset as soon as she joined the Company. She recounts an experience of how she achieved results by leveraging her experience from her previous job.

 

‘In the process of applying a film coating to tablets and coloring them, we had an issue with the coating separating from the tablet. I set about solving this issue as the technical leader.

 

We knew that the cause was excessive moisturization on the surface of the tablets, but we had been unable to determine the moisture content threshold at which that separation began.

 

I compiled a hypothesis by gathering opinions from various viewpoints, including those of my colleagues and superiors in my department and the staff at the plant. Taking many different parameters into consideration, such as the moisture content when spraying the coating agent, the temperature inside the equipment, and air flow movements, I adopted an approach that combined statistical analysis and thermodynamic theory. In this way, I succeeded in quantifying the critical conditions for separation of the coating.

 

My sense is that the skills in multivariate analysis that I acquired at my previous job helped a great deal in solving this issue. Being able to use data to substantiate a problem that everybody had vaguely felt was a significant achievement.’

 

Chugai Pharmaceutical’s organizational culture that creates innovation lies behind Chikushi being able to demonstrate her presence from her very first days at the company. Chikushi has felt first-hand that the “frontier spirit,” one of the company’s core values, has become firmly embedded in Chugai Pharmaceutical.

 

‘This company has a culture in which no distinction is made between homegrown employees and mid-career hires, and everyone feels comfortable voicing their opinions. There was even a forum for mid-career hires to express their views on Chugai Pharmaceutical’s strong points and areas for improvement.

 

Another noteworthy point is that the company has been proactively investing in digital technologies. In addition to the company-wide promotion of digital transformation (DX), the company readily accepts proposals for the introduction of new technology. This gives us plenty of opportunities to take on advanced projects.

 

I also identify strongly with the company's approach of identifying trends in cutting-edge technology through the alliance with Roche and striving to maintain its global competitiveness.’

 

Chikushi has just entered her third year with Chugai Pharmaceutical. She reflects on her growth since joining the company.

 

‘In my previous job, I was focused entirely on the work in front of me, and there was no opportunity to pay attention to technological trends at other companies. However, since joining Chugai Pharmaceutical, my horizons have broadened significantly through the alliance with Roche. I have been able to nurture the ability to view the industry from a global perspective, such as analyzing the technological strengths of individual countries and companies. I consider this to be an area in which I have grown considerably.’

To be a presence that can continues to contribute to the development of innovative solid drug products that are unique to Chugai Pharmaceutical

Throughout her career, Chikushi has been working on the optimization of the manufacturing process for solid drug products. She talks about the highlights of engaging in drug product research.

 

‘The development of solid drug products is the process of converting powders with various physical properties into another form that can be easily taken by patients. Unlike liquid drug products, maintaining the homogeneity of the ingredients is a major challenge.

 

The process of developing solid drug products, in which the drug substance and additive powders are combined into a single product, involves a complex interweaving of many different factors. This includes the particle size and other powder properties of each substance, their toxicity, and the various characteristics of the manufacturing process. Aiming for drug products that are safe and effective for patients, we work to optimize these factors, which I find very rewarding.’

 

There are numerous technical challenges in the manufacturing process of solid drug products, such as tablet dissolution and absorption, as well as resistance to humidity, temperature, and other factors. She has a message for her future colleagues who will one day work alongside her to realize the creation of innovative new drugs.

 

‘A strong will and voice will be essential in order to explain your ideas and visions to members of Chugai Pharmaceutical and Roche and to build consensus. I look forward to people joining us who can draw in other stakeholders through constructive discussions to promote projects while emphasizing teamwork.’

 

Chikushi’s current goal is to launch on to the market those products that she has worked on. She also has a vision beyond that.

 

‘Since I joined the company, there have been no new products launched. My immediate mission is to deliver the products that I have been involved in developing to patients.

 

In the long term, even if a day comes when I am no longer a researcher, I hope to stay involved in pharmaceutical technology. My goal is to make the most of the skills and experience that I have accumulated through my career so far and to continue to work actively in Chugai Pharmaceutical for many years to come.’