TAIPEI, Taiwan – Biopharmaceutical companies, both in the novel drug and biosimilar spaces, are facing long waits for investigational new drug application (IND) approval in China from the CFDA, delays that are slowly stifling the industry. That's according to panelists at a discussion on Taiwan-China partnership issues that took place at the recently concluded Biologics World Taiwan 2015 conference. Along with restrictions around the manufacturing of clinical trial and commercial quantities, it's making life tough for foreign and local companies alike trying to get a biologic approved and produced in China. However, these conditions are enabling Taiwan to step up and position itself as a better alternative for drug innovation and development activities.

Scott Liu, president and CEO of Shanghai Henlius Biotech Co. Ltd., spoke on some of these issues. Liu, originally from Taiwan, formed Henlius Biopharmaceuticals Inc., of Fremont, Calif., in the U.S. in 2009, and moved the company to China after joining with Shanghai Fosun Pharmacy later in the same year to become Henlius Biotech. His company has five innovative products in the pipeline, including one biobetter, with all assets developed in-house. According to Liu, IND filings will soon be made with the FDA, the TFDA (Taiwan) and the CFDA, the first to be filed toward the end of this year. And while ground has just been broken on a new manufacturing plant in Shanghai, the company intends to maintain an innovation base in Taiwan.

"We still think innovative research in Taiwan is the more productive option, because in China it takes at least two years to get IND approval. That's the biggest problem there; the regulatory process is suffocating the industry," said Liu. And in his opinion, Taiwan stands out in comparison.

"If you ask me what the biggest achievement has been over the past 15 years in Taiwan, I would say it's what the CDE [Center for Drug Evaluation, part of the TFDA] has put into place; setting up a regulatory system according to international standards, with a customer-oriented mentality, offering in-time, professional services to the industry," said Liu.

Racho Jordanov, CEO of Hsinchu, Taiwan-based drug development and CMO firm JHL Biotech Inc., explained how there are ways to take some benefit out of the differences in approval times.

"Our idea is to submit the INDs at these agencies at the same time. Submit in China, and submit in Taiwan or another country. While the IND in China is being reviewed, because of the excellent response that we get from the TFDA we will already have in our hand human data from phase I. And we can supplement our China IND submission with this data."

Eric Tsao, president of Synermore Biologics, of Taipei, described the three-country strategy his firm takes; running process development in Beijing and manufacturing in Shenzhen, with the quality good enough to enter a clinical trial in the U.S., according to Tsao. Then it files for IND and running a phase I trial in the U.S., but brings the product back to Taiwan for phase II studies.

"And while we file IND in U.S. we also file in China almost simultaneously, and by the time the Chinese CDE come back with review questions, we've already finished phase I somewhere else and hopefully that will facilitate the approval," explained Tsao.

NO CMOs ALLOWED

Another restrictive requirement is around manufacturing. Overseas firms wanting to run clinical trials and register their biologic drugs in China already face the requirement that all clinical and commercial quantities must be manufactured within China itself. But for local biologic drug development companies, an equally severe requirement states that aside from phase I and II batches, commercial qualities must be manufactured by the development company itself; no contract manufacturing organizations (CMO) allowed. This means that such firms need to commit to setting up their own plants at an earlier stage than they might otherwise be ready for, or be able to afford.

Lin Dou-Chang, chief technology officer, biologic R&D, for Hong Kong-listed Luye Pharma Group, of Beijing, explained how that puts his company, and others like it, in a very tough place.

"There are some rumors that in three to five years the CFDA will relax this rule just a little bit. But we cannot wait three to five years and find out we still cannot use a CMO. Right now we predict that our very first product will probably come to market in 2020 . . . an antibody product. We need to decide if we will need our own manufacturing plant, and if so, we need to start building now. It's already getting late. I don't have a really good answer on what's the best approach," he said.

Unless this requirement is relaxed, in the longer term it will probably force smaller firms to merge with larger ones so as to share the high cost of building a biopharmaceutical manufacturing plant.

Panel moderator Chi Wei-Kuang, director of the Bioengineering Group, Development Center for Biotechnology, of New Taipei City, closed the discussion with the observation that this would also indirectly affect Taiwan.

"With the necessity for every biologics drug firm to eventually become a manufacturing company, more facilities will be built in China. Then the problem for Taiwan will be in competing for a limited supply of talent," he said.

Biologics World Taiwan is an annual biopharmaceutical-focused meeting run by Singapore-headquartered events firm Imapac Pte. Ltd., part of a series of conferences that includes Biologics World Korea and Biosimilars World China.