Manufacturing issues in the time of pandemic is a recurring theme that was discussed in a recent high-level online forum organized by WuXi AppTec. Second in its series, the forum featured Johan Van Hoof, global therapeutic area head of the vaccines program at Janssen Pharmaceuticals R&D, which has invested in its manufacturing capacity with an eye toward one billion doses while controlling the cost to as low as $10 per unit. Phil Pang, chief medical officer of Vir Biotechnology, made an appearance too, talking about the company’s parallel deals with four different partners to make sure its anti-SARS-CoV-2 monoclonal antibodies will get made when needed in different stages of the development and commercialization process.
WuXi Biologics is one of the companies that has signed deals with Vir. The company resumed operation in its three sites, Shanghai, Suzhou, and Wuxi, after the extended Chinese New Year holiday as early as February 12, when most of the country’s businesses were still in lockdown mode. Pang said in the forum that WuXi Bio is helping Vir to get into the clinic in China as soon as possible, shortening the process that usually takes 12–15 months down to 3–5 months.
How do companies like WuXi Bio keep up its business activities critical to end the pandemic while ensuring employees’ safety and reducing any risks? Besides implementing twice-a-day temperature checks, and distributing PPEs to employees for daily use, WuXi Bio has developed emergency digital solutions using platforms such as WeChat and Dingding to support employees reporting their location and health status.
With the digital tools, the employees can also apply for a so-called “work permit” based on government and company policies, according to a written statement provided to GEN by the company’s public relations office. Over 99% of employees have been back to work, a spokesperson says.
Since February, the company has also been providing quality statements for each batch of product, certifying that no manufacturing or shipping personnel have reported suspected or confirmed cases of COVID-19.
To minimize potential transmission during mealtime, a new cafeteria configuration was put into place. Tables are six feet apart, and staff members are encouraged to come to the dining halls at different times to avoid gathering in large groups. Policies also include no talking, one person per table, “face to back” positioning, and keeping more than 1 m interpersonal distance.
WuXi Bio is not alone in taking strict measures to minimize risks involving COVID-19 transmission at the workplace. Abcam has put half of its workforce carrying out manufacturing, logistics, and essential lab work in China on split shifts, to maintain distancing between employees, as reported by Bloomberg.
And cautious measures are a common phenomenon now in many parts of the reopened country. At the OmniVision Tech Park in Shanghai’s Pudong New District, business has mostly gone back to normal. Only masks on everybody’s face and temperature checks at the gate of the park are reminding people that they are still under the cloud of COVID-19. The park complex also has a special health QR code for entry.
Going in to work on the eighth floor of the West Tower building, staff of I-Mab Biopharma need to sign in again at the entrance of the lobby and have their temperature checked for a second time.
Joan Shen, CEO of I-Mab, went through the temperature checks twice to get to her office, before talking to GEN’s reporter over the phone on April 20. The country’s COVID-19 data that day: Twelve newly confirmed cased were reported, of which eight were imported cases.
“We have a very detailed record of who has been in the building every day, and who has come into the complex,” she says. The safety of employees scattered around the world in Shanghai, Beijing, and Rockville, MD, has been her priority from the beginning of the outbreak.
Because of the experience operating globally, the immunology-oncology-focused biotech company was able to react quickly to the COVID-19 outbreak. At the beginning of April, it received an IND clearance from the FDA to run a three-arm, double-blind clinical trial in the United States on its neutralizing antibody TJM2 to treat cytokine storm or cytokine release syndrome seen in severely-ill coronavirus patients.
“Our [antibody] is for treating [these] patients, either by alleviating their symptoms or to stop them from having the cytokine release syndrome,” Shen says, which is usually irreversible and could cause organ failure and death. I-Mab has also submitted an IND for TJM2 in South Korea for an open-label clinical study.
Different from Roche’s Actemra (Tocilizumub) in its action of mechanism, TJM2 inhibits human GM-CSF (granulocyte-macrophage colony stimulating factor) to tamper an overactive immune system, instead of inhibiting the interleukin-6, IL-6.
GM-CSF sits on top of the molecular cascade that triggers the cytokine release; Shen explains. “So, if you switch off the GM-CSF, you have a much better chance preventing the rest of the cascade from going out of control. IL-6 is one of those.” I-Mab believes that a drug targeting GM-CSF may have a better efficacy than an IL-6 inhibitor, in theory.
None of the GM-CSF inhibitors have been approved, so TJM2 fits I-Mab’s first-in-class or best-in-class drug development portfolio.
Speaking of the trial in the United States, Shen says, “We are in the middle of recruiting patients, much faster than we expected. So, we had to accelerate the drug supply.”
Experts say under the cloud of COVID-19, shortages beyond PPEs and medical equipment are likely to occur, including things needed to make drugs and vaccines, as mentioned in a recent report from Fivethirtyeight.
Consider the glass vials that contain vaccines. As Van Hoof pointed out at WuXiAppTec’s second COVID-19 online forum, Janssen is considering packaging its novel coronavirus vaccines in multidose presentations, as one of the ways to keep the unit price low.
James Robinson, a veteran independent consultant in vaccine manufacturing who also serves as vice chair of the scientific advisory committee of CEPI (Coalition for Epidemic Preparedness Innovations), told Fivethirtyeight’s Maggie Koerth that, “[Janssen has] already preordered 250 million vials, and that might be all that’s out there.” CEPI is trying to procure another 200 million.
Luckily, for I-Mab, it has all the ingredients and the drug substances it needs at the CDMOs it partners with in China. “We were going to start the China study [for TJM2] anyway,” Shen points out to GEN. “We had an IND approval for other indications like rheumatoid arthritis. We need to do that study anyway so it’s an ongoing supply.”
Given the reduced number of airplane flights between continents, shipping could be another challenge for companies that need to move things around quickly. Shen says the company encountered some problem at customs, but it was eventually resolved. “Based on the timeline I’ve seen so far,” she adds, “if we ship out this week, they should get it early next week.”
When GEN spoke with her, I-Mab had its second batch of TJM2 at customs in China, waiting to be cleared for shipping.
COVID-19 is not the only disease being targeted by biopharma companies like I-Mab. Clinical trials for those diseases could be affected under the current environment as well, so careful planning is needed.
For example, I-Mab also has an anti-CD47 compound called TJC4 in two clinical studies for various cancer indications, one in the United States and in China. The first patient in China was supposed to be dosed right after the Chinese New Year, but the dosing didn’t happen until one month later.
Shen says the China study is almost back to normal speed from now on, but for the U.S. trial the company is trying to initiate more study sites as a backup to mitigate potential recruitment issue. “Fortunately, a majority of the sites are not in those populated cities like Chicago or New York. So, so far we have [seen] very minimal impact.”
For WuXi Bio, who is seeking to expand its global presence by building more overseas sites, the COVID-19 outbreak is causing a slight delay on that plan. Their Leverkusen, Germany plant, acquired from Bayer for final drug product manufacturing, is expected to launch in Q4 2020, according to the company’s 2019 annual results published in March, which is one quarter later than the original date revealed in an earlier document.
Besides the Germany plant, WuXi Bio has two manufacturing sites planned in Dundalk, Ireland, one is a drug substance facility and one is a vaccine facility. The vaccine facility, dedicated to “a global vaccine leader’s vaccine products,” will have an annual capacity of about 40 to 60 million vials, a spokesperson tells GEN. And it is expected to be operational in 2022, as stated in a press release published on February 18.
These sites are parts of WuXi Bio’s goal to build a secure and robust global supply chain network for its partners.
Although China has reopened its economy, those in the biopharma business recognized the uncertainty and the need to stay prepared. With TJM2, I-Mab plans to expand its study to treat patients with COVID-19 to China as well, after obtaining some data from the United States. “I believe the data we are generating in the United States will help to support our IND application in China,” Shen says, “as there are urgent needs to prepare for the next wave of outbreak of it happens.”