Scaling up to manufacture a massive volume of a COVID-19 vaccine, drug or innovative device that’s still in early stage development is easier said than done, especially in a global pandemic that has the supply chain stretched beyond capacity.
The urgency for a vaccine, diagnostics and treatments adds to the challenge, creating a new dynamic for industry. “Incredible scale and an incredibly quick pace – that’s hard to do,” Robert Spignesi, president and CEO of Rapid Micro Biosystems Inc., told BioWorld.
In the pre-pandemic world, vaccine makers had ample time to prepare the next seasonal flu vaccine, and sponsors of newly approved drugs and innovative devices were able to procure the supplies and manufacturing capacity needed to launch their products.
For those drugs and devices, demand grew gradually, enabling the sponsor to ramp up manufacturing over time in line with the demand, said Mike Piccarreta, a partner at global consulting firm Kearney who works with life sciences companies in sourcing and manufacturing problems.
With COVID-19 products, the demand will be huge at the outset, providing little time for scale-up. Consequently, companies are having to take a risk in securing that capacity before they even know if their product can live up to its perceived potential to take on the coronavirus, Piccarreta said. But there is a lot of competition for the limited capacity that’s available.
Given the volume of vaccines, drugs and diagnostics that are needed to address the global pandemic, “there’s just not enough capacity,” Piccarreta told BioWorld.
Handful of options
Sponsors have a handful of options. Each comes with public health trade-offs and sponsor risks, and some could take more time than what the pandemic provides.
An obvious option is to reserve capacity at external facilities such as a contract manufacturing organization (CMO) or another company that has excess capacity and the capability to manufacture the proposed product. The cost for that could go up as the demand exceeds the available space. One trade-off would be reduced capacity for manufacturing other products, which could then fall into shortage.
Another option is for a manufacturer to repurpose its facilities or convert lines from existing products. There are regulatory hurdles with that option, as well as the opportunity cost, especially if the product proves not to work against the coronavirus.
A third option is to build a new facility, Piccarreta said. Again, there would be regulatory hurdles and opportunity cost. There’s also a time factor. Building a new plant can take up to five years, which adds to the opportunity cost and risk.
In recent years, CMOs and large biopharma companies have invested in a lot of plant and site development for biologics and gene and cell therapies, Spignesi said, noting that “this is a global process.” However, the need for what could be billions of vaccine doses globally could crowd out some of that biologic manufacturing, he said.
Another way to address manufacturing capacity is to improve systems, reducing production times and automating quality systems to avoid contamination problems that could cause delays. As an example, Piccarreta pointed to what Gilead Sciences Inc. is doing to ramp up supplies of remdesivir, the first drug granted an FDA emergency use authorization to treat severe COVID-19 cases.
Besides building a consortium of manufacturing partners to help maximize the global supply of the antiviral, Gilead has invested in improving processes to shorten the manufacturing time for the drug. “The typical timeline for manufacturing a drug like remdesivir at scale is nine to 12 months; we have reduced that period to six to eight months,” the Foster City, Calif.-based company said earlier this month, adding that it is continuing to work to optimize “the chemical synthesis processes to further accelerate product deliveries and volumes.”
Because of the risks involved, some governments are stepping in to help sponsors meet the demands of a pandemic-sized scale-up. Just this week, the U.S. Biomedical Advanced Research and Development Authority’s (BARDA) announced a partnership with Astrazeneca plc, in which the government agency will support manufacturing scale-up, as well as advanced clinical development, for a recombinant adenovirus vaccine that the company plans to begin delivering in October.
While the Cambridge, U.K., company to date has booked orders to supply at least 400 million doses of the vaccine, of which 300 million doses will go to the U.S., it already has secured manufacturing capacity for 1 billion doses and is in discussions with the Serum Institute of India and other potential partners to further increase production.
Upstream and downstream
But scalability is more than manufacturing capacity for the finished product, Spignesi said. It also includes the capacity to manufacture all the raw materials and supplies that will be needed to produce, distribute and administer a vaccine, drug or diagnostic.
To meet the demands of the pandemic, sponsors are having to procure materials at an exponential volume, which is pressuring the capacity of their suppliers and their suppliers’ suppliers, Spignesi said. That puts a lot of strain on the upstream process. Then there are the downstream logistics that must be managed to ensure the products end up at the right place at the right time, along with all the supplies needed to administer them.
“If any part of that chain breaks down,” there will be a problem, Spignesi said. The U.S. already encountered that when COVID-19 testing began. The swabs needed for the test were produced in Italy, which had locked down to stop the spread of the coronavirus.
An added challenge in a global pandemic is the scale of competition for active pharmaceutical ingredients (APIs), supplies and finished products. With the existing capacity designed for normal output, companies are competing for a limited supply of specific APIs, glass vials, stoppers, needles, syringes, sample collection devices, etc. And countries are competing for the finished product, with some going so far as to restrict exports of certain medical products to ensure they have enough for their own public health needs.
As a result, the unprecedented global demand has made scaling up much more challenging and has plunged the industry into an unfamiliar world when it comes to the supply chain, Spignesi said.