Biopharmaceutical COVID-19Tonia Becker, Life Sciences Editor, Macon Raine, talks with BioTechLogic’s Dr. Mike Berry.

Knowing that BioTechLogic’s team of biopharmaceutical consultants is working with many companies in the industry to help speed the path to market, I was interested in learning what they see in the industry in light of the COVID-19 pandemic. Events are changing quickly as some states are loosening some restrictions; however, virtually all epidemiologists anticipate the need to fight the pandemic in waves. Already, much has been learned from this first wave that can be applied to the future. 

I had the opportunity to speak with Dr. Mike Berry, BioTechLogic senior consultant, Technical Operations, based in Eagle, Idaho. Here’s what he had to say.

What challenges are your clients facing as they continue their work?

Mike: BioTechLogic works with a broad spectrum of clients. Some are small with somewhat limited budgets, and some are large organizations with tens to hundreds of millions of dollars available to them. Of course, we are seeing that clients with fewer available resources need to be much more careful in terms of resource allocation. The biopharmaceutical, pharmaceutical, and medical device industries are moving forward as planned, but most everything has been slowed down. Clinical trials are being delayed, materials are more difficult to ship, and product manufacturing is more challenging. 

Here’s an example. We just produced the first engineering batch of a drug substance for one of my clients at a CMO. Because of the precautions we had to take, we were not allowed to have anyone from the BioTechLogic team or anyone from the tech transfer team on site at the CMO, let alone in the manufacturing suite. We had to get highly creative to develop protocols to make this work. 

We ended up building a phone list of contacts for each step in the manufacturing process. However, the operators on the floor were extremely isolated from anybody else involved in the project, and, as I said, no one from the tech transfer team was allowed in the plant. When the manufacturing team ran into issues, it was difficult to address the problems promptly. They experienced delays between when they could get hold of the primary contacts within their organization and when that person could contact the appropriate external person. The run did not go smoothly, but we got it done, and we learned some things. However, the situation was quite difficult.

For the most part, my clients are ticking along. Slowdowns are happening here and there due to the working conditions needed to deal with the pandemic, but much of the work in the industry is moving forward as planned.

Have your clients’ priorities been adjusted since the pandemic reached the US? What other dynamics are they working to manage?

Mike: Every company I work with is obviously trying to move its programs forward as quickly as possible. The speed needed to make materials and get them to the clinic is the priority for almost every organization. Most of the companies I’m working with already had materials in storage before the pandemic hit, which has helped keep things on track. 

However, one of the challenges I am seeing is access to CMOs. Some CMOs are already involved in COVID-19 programs working with companies that have already been funded—either through government funding or self-funding—to work on vaccines or therapeutics. There will be some delays in some plants for this reason. This said, we are not seeing the CMO access problem I was worried we were going to. 

I believe we are not seeing CMOs being bogged down because much of the grant money seems to be going to large companies with internal capabilities. For better or for worse, the government seems to be funding big pharma (J&J as an example) rather than smaller companies that might have more novel ideas. I’m a bit concerned about this because, by and large, big pharma has not developed vaccines for some of the more challenging viruses such as RSV even though they have been working on them for many years. I don’t know that they are going to be able to effectively flip a switch and start developing challenging vaccines that require a lot of innovative thinking. On the other hand, big pharma has a lot of resources at its disposal to tackle the problem.

Do you think the COVID-19 pandemic will cause us to think differently about how we approach vaccine development?

Mike: I don’t think the vaccine development dynamic will change because it really can’t. The challenge is that you don’t know what the virus is going to be until it strikes, and then you have to react quickly. Take seasonal influenza, for example. The CDC gets together in February and March and selects the strains that will be in the vaccine—quite frankly, it’s guesswork, and sometimes they do get it wrong. However, once the CDC has determined the strains, manufacturers then have to go full-throttle to manufacture vaccines for availability in pharmacies by August or September. Every single year, vaccine manufacturers make massive amounts of material in an incredibly short period.

Some years it is even more challenging—maybe the strains aren’t selected until April, and they end up being strains that are difficult to grow. There are not a lot of companies making vaccines because it is hard to do, and they are, by and large, very low-margin products.

COVID-19 vaccine development is moving forward rapidly. Do you have concerns as to what developers might encounter?

Mike: The proteins/antigens needed for the COVID-19 vaccine are not simple, and I fear that this will be a problem. The work that has been done to develop a vaccine antigen for the respiratory syncytial virus (RSV) might be helpful in showing us the challenges we will have to address. The RSV virus is incredibly dangerous for young children; in fact, it’s one of the biggest risks for premature babies. Teams have been working on RSV vaccines for decades and have really not got far yet with a protective vaccine. We basically know what we have to manufacture, the RSV F antigen but we can’t make it because it’s extremely difficult to scale and has very poor yield. The F protein needed for an RSV vaccine is very similar to the protein needed for a COVID-19 vaccine because scientists found the same kind of structure is involved in the surface protein of the COVID-19 virus as the protein on the surface of RSV. 

For COVID-19, it’s called spike  or S protein, and for RSV it’s the fusion or F protein, but essentially it has the same structure. It does the work of attaching the virus to the cells; then, it gets clipped so the virus can enter the cells. The problem is that there is a whole series of events in virus adsorption and entry to cells, and the proteins are normally very easily clipped. So you have to mutate the protein to make it stable to be able to be expressed at all, and when you do that, it often can’t be expressed easily, leading to substantial yield problems. If we must make this particular S protein, it’s going to be a big challenge. How will we vaccinate 350 million people? We are going to have to resolve this problem.

Given the supply chain risks posed by the pandemic, do you expect any movement toward reshoring API manufacturing or reshoring some of the final dose manufacturing that has been outsourced?

Mike: While this is an interesting question, I don’t think any company is going to change its plans right now. The industry will only change if huge global supply chain disruptions become a reoccurring problem. 

 

If your team is challenged by hitting pending deadlines, BioTechLogic’s team of expert, senior-level consultants are happy to work alongside your team to make sure you hit your critical milestones. Feel free to contact us.