BioProcess Insider brings the news as it breaks. At the BPI Theater @BIO, editor Dan Stanton conducted a series of interviews live on stage to report on the latest movements in the biomanufacturing industry to start each busy day of dealmaking in Boston. Below we summarize his DAY ONE conversations with a number of biopharmaceutical executives on Tuesday 5 June 2018. You can watch the full interviews online at www.bioprocessintl.com/BIO-Theater-2018.
Andy Topping, Chief Scientific Officer, Fujifilm Diosynth Biotechnologies
Gene therapies show great promise, and future demand is growing. Current manufacturing capabilities are not adequate to keep up with current demand. Contract manufacturing organizations (CMOs) such as FDB are running to keep up with new products. New companies are looking for early phase services. Early phase manufacturing isn’t really manufacturing per se; it entails laboratory processes performed in a different environment. The laboratory environment is challenging for making enough of these products even for early clinical development.
FBD started looking into gene therapies in 2014 when it acquired Kalon Biotherapeutics, a viral vaccine company. Although FBD still supports viral vaccines for pathogens, it is increasingly using those facilities to produce gene therapy vectors because the technology is very similar.
One of the real challenges for gene therapy manufacturing is how to make enough product. If you’re using adherent cell culture technology, for example with HYPERStack cell culture vessels, and attempting to scale out, it quickly becomes very difficult if you want to treat more than a few hundred patients. For instance, FDB runs some processes that use 50 HYPERStack units per batch. But procuring enough HYPERStack hardware is a current issue for the industry, which speaks to the explosion of early phase manufacturing and illustrates how cumbersome these laboratory processes are compared with real manufacturing processes. Using HYPERStack systems requires complicated manual handling. If the company could switch to a suspension cell culture, it could get five times more product from about a 2-L suspension culture cell line. Eventually, after switching to a suspension culture, you could use a 2,000-L bioreactor, an option that will be available in FDB’s new Texas facility.
Dave Kenyon, Senior Director of Global Scientific and Technical Affairs, Patheon Biologics
Throughout our network, we are seeing an increase in capacity needs for biologic products, both in the United States and overseas, and single-use technology is the key to supplying a range of products to the market. Many customers are developing novel therapies for unmet needs, and having single-use capability allows them to switch over very quickly, scale up and down as the market changes, and ensure a low risk of cross contamination. Patheon is investing $50 million in facility upgrades and expansion that will be doubling its manufacturing capacity and will continue to expand as the need arises. We are building a smart factory that allows us to gather data throughout the process and produces data very quickly and efficiently.
ThermoFisher Scientific provides support for the market across the biotechnology industry, so whether for analytical complexities or diagnostics or pharma services, it has a strong infrastructure. This gives the newly acquired Patheon a substantial reservoir of resources in technology, subject matter experts, ability to meeting market demands, and general support. ThermoFisher will remain our suppliers, and Patheon will use ThermoFisher bioreactors. Customers with later stage projects that have been using different equipment have no need to worry about transferring technologies halfway through. We have been successful in moving clients from glass reactors to singleuse reactors and across different systems.
Both from a statistical point of view and from the field, clients say that there is a strong need to increase the pace and accelerate manufacturing products for first-in-human trials. Patheon has devised a program that streamlines the supply chain and produces clinical material as part of its “quick to clinic” strategy.
ThermoFisher is looking into new therapies and new ways to treat unmet needs. In time, we will be providing additional support for different types of modalities.
Kevin Noonan, Partner, McDonnell Boehnen Hulbert & Berghoff LLP
In discussing how litigation has restricted the approvals of biosimilars, we find that it has not. Congress intentionally didn’t set up biosimilar litigation schedules like it did for the Hatch–Waxman Act (1984) for small-molecule generics. Biologics have a much longer time of exclusivity. A small-molecule drug has five years of exclusivity. In addition to the life of a patent, coverage is extended by a portion of the time a drug is under regulatory review by the FDA.
For biopharmaceuticals, patent exclusivity is 12 years from the time of biologics license application (BLA) filing. With four years for approval, you get eight more years. Congress says that in those eight years the parties can litigate to determine the first wave of patents that could prevent biosimilar drugs from coming onto the market at the 12-year mark. But most biosimilar applications are for drugs that have been on the market for a long time and have been approved much more quickly than anticipated. That is because the FDA decided to accept European testing data, so the drugs made it to market much quicker.
Instead of what Congress anticipated, companies have ended up doing a “patent dance.” One side presents the patents it expects to be infringed, and the other side presents why those patents won’t be infringed, and they negotiate until they get down to one or two patents to litigate. However, Sandoz has found “a clever legal technique” to forestall that, and the US Supreme Court agreed in a 2017 decision that it could bring treatments to market immediately upon FDA approval — without waiting an additional six months.
Also in 2017, Amgen reached a settlement with AbbVie to delay the US launch of the biosimilar competitor for AbbVie’s blockbuster rheumatoid arthritis drug (Humira) until 31 January 2023. In this case, an innovator had invested a great deal of money into its drug and into the market. For it to be challenged by a generic of any kind meant that a lot of money could be made and a lot of money could be lost. If a biosimilar manufacturer loses such a lawsuit, then its product will be off the market until the patents expire, which in this case would be much later than 2023. On the other hand, an innovator might be willing to trade exclusivity for the certainty of knowing when a biosimilar is coming to market.
European countries do not run into the same patent litigation concerns because their governments are more closely involved in these endeavors. European governments prioritize biosimilars and an end to innovators’ market exclusivity as a way to get drug prices down.
Rory Mullen, Vice President of New Business, IDA Ireland
Irish companies have manufactured small molecules for a long time and retain a reputation for high-quality products. A large part of Ireland’s economic development strategy is to attract new and exciting companies to the country, with the biotechnology industry recognized as a key target. We have been successful in the technology space and life sciences in particular. Many large companies have facilities at multiple sites, so when the biopharmaceutical industry as a whole increased its investment, Ireland specifically set out to attract some of that by ensuring that we had the infrastructure and necessary skills available.
The Industrial Development Authority (IDA) of Ireland divides the life-science industry into three main areas: small-molecule manufacturing, large-molecule manufacturing, and biotechnical services. The latter is growing the most quickly. We have seen huge growth in biologics manufacturing for both drug substances and drug products. Although some classical pharmaceutical facilities closed their doors a few years ago, we have maintained many of those sites and repurposed them for biologics.
The Irish government supports training and upscaling in this industry by supporting multiple programs that people can enter to learn new techniques and technologies for working with large molecules. IDA Ireland works with institutes and colleges across Ireland to ensure that the pipeline of skilled people will be filled.
The United Kingdom is our closest ally and partner in the European Union, and we are sorry to see it leave through “Brexit.” We would prefer that it reconsider that decision. There might be some opportunities in which we seek to compete with our UK neighbors, but we hope for them the softest Brexit possible. Our challenge will be to remain close allies with the United Kingdom while remaining an integral part of Europe.
Ireland has a competitive tax rate because, regardless of what happens at the Organization for Economic Cooperation and Development (OECD) level, we need to have a competitive tax rate with the United States. Combined with an excellent operating environment and the availability of skilled people, that forms a large part of our value proposition. Tax rates are only a part of that. The business-friendly environment, availability of skilled workers, and active and forward-thinking managers are what encourage businesses to come to Ireland.