The FINANCIAL — Lilly is creating and testing neutralizing antibodies that target the viral spike protein that SARS-CoV-2 uses to gain entry into host cells. These treatments are specifically designed to treat COVID-19 and require specialized people – such as scientists and engineers – and nearly 300,000 square feet of manufacturing space, 40 miles of piping, 50 processing vessels, and several controlled environments such as cleanrooms to manufacture.
It can take up to 90 days to manufacture a single batch of the active pharmaceutical ingredient and drug product for a neutralizing antibody for COVID-19. This is due to the highly complex manufacturing processes, with carefully controlled conditions and numerous quality and safety checks.
Here’s a closer look at what it takes to get a neutralizing antibody from the lab to a manufacturing site and, finally, to patients:
Cell Culture Growth and Production
Lilly starts with a frozen vial – less than 1 inch in size – containing 10 million cells of the active protein and host cell. Once thawed, the cells are fed and grow to over 250 trillion cells – that is over seven times the number of cells, 35 trillion, in a human body. During this time, it’s critically important to avoid uncontrolled growth, so the cells are moved to larger sterile vessels gradually, from 1-mL vials to 15,000-L bioreactors.
After growing for up to 20 days, the cells then start to secrete and produce the active protein. The production of the active protein can take 14 to 20 days. It takes approximately 350 mL of cell culture to make one single dose of a neutralizing antibody.
The active protein that is secreted from the cells is purified and packaged before ultimately becoming the solution that is infused through an IV. But there are still several steps to complete, including recovery of the active protein. This recovery process can take 14 to 20 days.
Recovery and Purification
The active protein is separated from the host cell and purified to remove all process related impurities to meet the desired quality and concentration. This solution of active protein is then shipped to a different manufacturing site in sterile, temperature-controlled containers for formulation and filling.
Formulation, Filling and Packaging
During the formulation process, the active protein is mixed with a buffer solution to reach appropriate concentration of the product and ensure it is stable and compatible with the biochemistry of patients. This is then filtered to remove any bacteria or particles before moving on to the filling process.
To continue to keep the solution free of bacteria or other particles, the automated filling line is monitored by certified operators trained in practices that ensure a sanitary environment. The solution is transferred to vials and sealed, then rigorously inspected, labeled and packaged, before finally being ready for patient use.
Usually it would take months or even years to prepare for and fully complete this process, and company would not begin large-scale production until it knows that a medicine is efficacious and will likely be approved for use.
To help meet the urgent need and global demand for a potential COVID-19 treatment, the company expedited manufacturing process – without compromising quality and safety standards – by initiating large-scale production at risk when Lilly’s first human clinical trials began.
