Editor's Note:
In July of 2012, Dr. Dou Changlin, an expert in antibody technology who has worked in the U.S. and Singapore for over 20 years returned to China to participate in the establishment of Boan Biotech. In November of the same year, Boan Biotech kicked off the Avastin® biosimilar project. With 8 years of efforts, 博优诺®(Bevacizumab Injection) was granted with marketing authorization. 博优诺® is the third biosimilar of Avastin® to enter the market in China, as well as the first product from Boan Biotech’s pipeline to receive marketing authorization. Through the development of 博优诺®, Boan has further proved its R&D and manufacturing capability in biopharmaceuticals. As one of the important strategic directions for the current and future development of Luye Pharma, the biopharmaceuticals represented by 博优诺® will help the company accelerate the global planning of its biopharmaceutical business. This month we invited the head of this project, Dr. Dou Changlin, R & D President and COO of Boan Biotech to share with us the background story of 博优诺®.
Dr. Dou Changlin- President of R & D and COO of Boan Biotech
Dr. Dou holds a PhD in Neurobiology from Stony Brook University. Mr. Dou has 30+ years of research experience in antibody development, he is the former CTO of A-BIO, and former Senior Scientists at Regeneron and Genentech.
Q： Hello, Dr. Dou, thank you very much for accepting this interview. We have read a number of good news about 博优诺® (Bevacizumab Injection) recently: the successful product launch in China, the first prescription written in multiple Chinese hospitals, and Boan Biotech grants AstraZeneca exclusive rights in specific county markets of China. As the head of this project, could you please start with a brief introduction on the progress of this project and its background?
D: We kicked off the project in November of 2012, and received marketing authorization in April of 2021, which takes approximately 8.5 years. The overall development progress was quite smooth, we were able to launch the product 1.5 years ahead of timeline, which is also shorter than average development period of antibody drugs (10 years). Important milestones during the development include: IND submission, clinical trial approval, clinical study, manufacturing process validation, BLA submission, on-site inspection, on-site inspection on clinical research, registration of samples, and marketing authorization. We completed all pre-clinical pharmacology study and non-clinical study 2 years after project initiation. We submitted IND in October, 2014 and was granted with clinical trial approval in September, 2016. Then we initiated Phase I and III clinical studies, as well as process specification and validation. We made every effort to promote clinical studies, accelerate pharmacology studies, strengthen coordination among different departments. We filed NDA 8 months ahead of schedule, and avoided the new edition of ‘Measures for the Administration of Drug Registration’ which might delay review period. We started gap analysis on application documents while we were waiting for CDE’s first round of feedback, so that we can be ready for supplementary documents in advance. And that is why we can submit supplementary documents to the authority in a very short period time when we receive the notice in October of 2020. We used scientific methods to arrange manufacturing schedule, and when we received notice on on-site inspection, we can arrange dynamic manufacturing immediately. We finished the dynamic manufacturing and packaging of 3 batches, and send it to drug control institute overnight. We had comprehensive communication and swift actions during the whole process, and only used 12.5 months to finish the registration.
Q: 博优诺® is the third biosimilar of Avastin® to enter the Chinese market, in order to achieve that, in addition to use innovative methods to get ahead of competitors during application process, Boan’s R & D capabilities also play a vital role, what do you think the core competitiveness of Boan’s R & D platform?
D: It is not accidentally to accelerate product development and registration. The success of this project is due to the solid technology foundation we have laid since the establishment of Boan. Our core competitiveness lies in high level of R & D capabilities and practical CMC. We have consistent process development to ensure the consistency of product quality. The team is equipped with strong execution and extensive practical experience in process scale-up and tech transfer.
We have experienced 2 tech transfers and site changes during the process. We completed manufacturing process transfer from 200L (Boan) to 2000L (CMO) with just one time in 3 months. We had to make a tough decision in 2018: 1) transfer the commercial manufacturing site from CMO back to Boan, which will face risks in site change and registration; 2) use CMO to file NDA, which will face high manufacturing cost. And finally we decided to go with option 1 due to our confidence in product process and technical team’s capability, we were managed to finish the transfer with just one time, which saved 100 million RMB in process validation and dynamic inspection and strengthened 博优诺® ‘s competitiveness. We have achieved 100% of success rate in the 8 batches of 2000L samples produced in Boan.
The launch of 博优诺® proved our solid capability in pharmacology research. In terms of technology innovation, Boan has established platforms including human antibody transgenic mouse, bispecific T-cell engager, ADC. The combination of efficient innovation and practical CMC have enabled Boan’s core competitiveness.
Q: The success of 博优诺® is due to the project team’s hard work, what is your view on teamwork to a successful project?
D: This is a very good question. The process of antibody drug development is very difficult. We need both team members’ expertise and good collaboration for efficient operation. We have different roles including antibody screening, cell line development, lab-scale process development, pilot-scale process development, manufacturing scale-up, analysis, pharmacology, toxicology, PK, clinical, quality, registration and sales to work together as a team. We conducted smooth communication and strictly execute the work plans we have made., because collaboration is the key to a successful project.
Since the establishment of Luye Pharma in 1994, the company has built up excellent expert team and valuable experience in R & D, manufacturing, quality, workshop construction, government affair and others. Boan is able to achieve efficient operation with the strong support of Luye Pharma.
Q: Do you have any memorable stories about teamwork to share with us?
D: I have two stories to share with you. When we were working with CMO on the manufacturing of clinical samples in the summer of 2017, everything went quite well with stock solution, but we discovered deviation during filling, which caused increasing number of faulty preparation products and is in the risk of delay clinical progress. I took my team to visit CMO immediately and started in-depth communication to find a solution. After a series of research, we managed to close the deviation and secured the progress of clinical trials.
The second story happened after we started Phase III clinical studies. We were facing fierce competition for clinical resources during that time. President Yang attended R & D’s quarterly meeting in September, 2018 in Changbai Mountain. He discussed with Dr. Li, the commercial operation team and me on how to accelerate this project through cross-functional collaboration. With the great support from Group R & D and operation department, we were able to speed up clinical studies and became the third company to bring this product to Chinese market.
Q: 博优诺® is the first product that obtained marketing approval in Boan Biotech’s product pipeline, what does this mean to Boan and future pipeline?
D: The success of this project proves that Boan Biotech is a comprehensive company equipped with capabilities in biopharmaceutical R & D and commercialization that covers the whole life cycle of drugs. Boan is at forefront of the competition among hundreds of biopharmaceutical companies in China.
The review and approval standards of NMPA are very high, especially the approval of biosimilar drugs is required to achieve a high degree of consistency in pharmacology, non-clinical, clinical with the originator, and the regulations have been aligned with Europe and the United States. This is a challenge but also an opportunity to Boan, because we have the capability and strength to launch more products. We are going to focus on global launch of LY06006 and LY01011 as the next step and develop global strategic plans for other product in our pipeline step by step.
Q: What is the future plan and expectation on 博优诺® and research pipeline? What is Boan Biotech’s global strategy?
D: Pharmaceutical companies need global strategic planning, and so does Boan. We are currently doing research on 博优诺®’s market potential in emerging countries and we are already in conversation with some countries. We have started phase Ⅰclinical trials of LY06006 and LY01011 in Europe and the U.S., and Japan is also involved in our development plan. We have over half of innovative antibodies in Boan’s research pipeline. The internationalization of biosimilar and innovative antibodies is based on forecast of each product in target market. During the application in China and oversea market, we also constantly make improvement plans,
Q: Luye colleagues across the globe have celebrated Luye’s 27th anniversary last week, we have heard your speech on 博优诺® during the celebration. In three years’ time, Luye will celebrate its 30th birthday, what is your expectations for the future of the company?
D: With 27 years of development, Luye Pharma has become an international company with global R & D, manufacturing and marketing as strategic focus, and has already developed important products in CNS, oncology and other areas.
I always say biopharmaceutical is an important direction of pharmaceutical companies. Aside from our pillar products, Boan has started to make strategic plans in new areas in the recent years, including cell therapy, ADC drug and some other new technologies. We hope these new technologies and development can bring diversified development and abundant return. Luye has set a vision to become global top 50 pharmaceutical company by 2025, I hope Boan can make its own contribution to support the company to achieve this vision, and I hope Luye can have splendid future.
