The demand for vaccine, cell and gene therapeutics, and biologic manufacturing has increased dramatically in recent years, in part due to the need to produce billions of doses of COVID-19 vaccines and therapeutics. IDT Biologika, a CDMO largely focused on integrated vaccine manufacturing from process development to final product packaging, has responded with notable investments in greater drug substance, drug product, visual inspection, and packaging capacity, leveraging state-of-the-art automation technologies and supported by additional investments in ancillary storage and handling capabilities. Prof. Dr. Ulrike Fiedler, Chief Commercial Officer at IDT Biologika, discusses the drivers of the investment and what might be coming for the industry and IDT Biologika in the near future with David Alvaro, Ph.D., Pharma’s Almanac’s Editor in Chief.
David Alvaro (DA): In light of the big milestone passed last year, can you share an overview of IDT Biologika’s long history and the key moments that brought the company to where it is today?
Ulrike Fiedler (UF): IDT Biologika celebrated its one hundredth anniversary in 2021. Due to the COVID-19 pandemic, we did not have a big celebration, but we did delve into the company’s history to really look at what has been achieved during those years.
The company was started 100 years ago in Dessau, Germany, on a site just a few kilometers from our current location, as Bakteriologisches Institut der Anhaltischen Kreise (Bacteriological Institute of the Anhalt County). Its purpose was to meet the need for human and veterinary vaccines following World War I. The first focus was on tuberculosis, which affected not only humans but cattle. The production of other vaccines and sera began on a laboratory scale just a few years later and shortly thereafter in larger quantities. In 1935, the company developed a vaccine against diphtheria in humans, and vaccines against cholera and whooping cough followed.
Much growth and change occurred over the next decades, particularly during the time that the company was located within the Soviet zone of occupation and the German Democratic Republic (GDR). Several vaccines to treat both animals and humans were developed, as well as related products, such as a hepatitis B detection test. By the late 1970s, the company was producing over 100 products and was eventually renamed Impfstoffwerk Dessau-Tornau, supplying all Eastern European socialist states with products while also exporting products to the West.
Immediately following the collapse of the GDR and the reunification of Germany, the company had approximately 1,500 employees. The company struggled, however, and the number fell to around 200. We were then acquired by a private entrepreneur in the packaging industry from the Western part of Germany who saw the potential of the company’s rabies vaccine. IDT Biologika eventually emerged from that investment and has since grown back to 1,600 employees. We are still privately owned, and with such minimal hierarchy we are able to make quick business decisions.
Our headquarters are still in Dessau, but we also have a site focused on process development and phase I and II manufacturing in the United States in Rockville, Maryland. Today, we are focused on providing contract development and manufacturing services for human vaccines, but also cell and gene therapies and oncolytic viruses. We also perform fill-finish for a variety of other biologic products, such as RNA therapeutics and mAbs. We support clients from process development through drug substance manufacturing, formulation, filling, labeling, and packaging, with all of that work supported by a large quality control department. As a result, we offer customers true end-to-end services.
DA: How has IDT Biologika been transformed by COVID-19 and the burst in interest in and demand for vaccines?
UF: IDT was manufacturing vaccines with FDA and EMA approval for a long time before the COVID-19 pandemic emerged. We continually put this unparalleled experience to work for our customers and in the last two decades have been involved in the development and production of vaccines against infectious diseases such as influenza, smallpox, HIV/AIDS, malaria, Ebola, Chikungunya, Lassa fever, and Dengue fever. Due to the COVID-19 pandemic and the large focus on vaccine manufacturing, IDT has gotten more exposure as a producer of Janssen and AstraZeneca’s vaccines. We also have another product online today for the Austrian company Valneva.
DA: Which of the markets that IDT is involved in — vaccines, cell and gene therapy, fill-finish for biologics, and so on — do you see as the most dynamic and presenting the greatest opportunities in the short to medium term versus those that are more stable and will have longer staying power?
UF: We are actually basically in three markets. The vaccine market is a growing market, with the annual growth rate approximately 10% prior to the COVID-19 pandemic. The market nearly doubled in 2021; however, due to the demand for the COVID-19 vaccines. It is difficult to foresee what will happen in the future, but we do expect there to be greater focus on vaccines than in the past and thus continued healthy growth. It is of course a market we have been in for more or less 100 years and definitely our market in the future.
Cell and gene therapy (CGT) is our second market. The growth of this sector is much higher and was foreseen to be about 28% annually. Several companies, however, have switched their focus to COVID-19 treatments, so the growth rate has dropped somewhat. We expect this decline to be temporary though, and the strong growth will return. The CGT space is quite crowded, with both a lot of product development occurring and a lot of CDMOs being established as well.
Our third market is the biologics market, which is dominated by monoclonal antibodies. The market is still growing but at rates much lower than that seen for cell and gene therapy. Even so, we expect to see steady growth.
DA: Have there been any shifts in what companies are looking for in a vaccine CDMO?
UF: We have several different types of customers. The large pharmaceutical companies expect high quality, often beyond what is required by the regulations. IDT has the same very high quality standards and has demonstrated our ability to meet these high expectations. A second important topic for these customers is security of supply — that as a CDMO we can deliver that high-quality product on time every time. These are the two key parameters for the larger companies, and IDT has invested a lot in the last year to position the company at the top. For instance, despite the pandemic, we were able to really deliver the vaccines on time as agreed upon with our customers: not a single day late.
We also have many biotech companies as customers. Of course, these customers also focus on quality, but they are also driven significantly by time to market. To support these clients, therefore, it is necessary to help them get into the clinic as fast as possible and to provide assistance with writing documents and other ancillary activities.
Finally, we also have the government as a customer, which is a little bit different, because the relationship is more formal, and there is more prerequisite work.
DA: With regard to the recent expansion at IDT Biologika, can you give me an overview of the key drivers for this investment?
UF: Since our last investment in commercial manufacturing some years ago, which involved both drug substance and drug product manufacturing, we have seen growing demand in the market. Both our drug product (fill-finish) and drug substance suites were fully booked, and we were not able to supply our existing customers with additional slots or take on any new customers.
Fill-finish demand was particularly high during the COVID-19 pandemic, and, although a couple of customers were willing to give up their slots to COVID-19 products, that was always a difficult discussion. In the end, a number of new companies entered the market and offered capacity, but not all of them have been successful, because sterile filling is complex and requires extensive experience to implement properly. Some Big Pharma companies have also offered idle filling capacity to support COVID-19 products.
As a result, today there is a lot more fill/finish capacity than there was before the pandemic. It will be interesting to see how much remains onstream once the pandemic is resolved — whether there will be overcapacity or some companies will choose to withdraw. Regardless, IDT will be positioned to support our customers across both drug substance and drug product manufacturing, which helps them eliminate the additional cost, time, and complexity by using IDT’s technological variety, know-how, flexibility, and expertise in global markets.
DA: What can you tell me about the scope and scale of the expansion?
UF: Before the pandemic, we already had construction underway to enlarge our commercial capacity for different drug substance technologies. We are now further expanding drug substance capacity for suspension cells. The new building will house up to 6 x 2,000-L bioreactors (STR) at Biosafety Level (BSL) 2 for up to 165 batches per year. The seven suites of the building allow for flexibility in upstream and downstream technologies and are customizable at clients’ demand. In fact, we have adopted a modular concept that makes it possible to work with 2,000 or 4,000 L or even 12,000 L. They are designed to support suspension cell culture or iCellis, but not any specific type of product, including viral vaccines or viral vectors. Moreover, we upgraded another suite to BSL-3, mainly to be used for commercial manufacturing with iCellis technology.
For drug product manufacturing, we had the design for a new filling line already developed before the COVID-19 pandemic, and it is one of the most modern in Europe. The high-speed filling line can fill 32,000 vials per hour with 100% filling and crimping control and batch sizes of 500,000 vials 2R. It is also flexible, allowing the filling of different formats as 2R, 6R and 10R.
Furthermore, we are installing a new automated visual inspection system with the line that can inspect approximately 36,000 vials per hour, enabling faster product release at lower cost. This line will complement the additional midsize and small-scale filling lines that we already have in place for commercial manufacturing of smaller numbers of vials and syringes, such as for cell and gene therapies.
It is important to note that we also provide new packaging capacities to support the expected larger number of vials. This includes labeling and automation as well as highly flexible manual packaging of vials, pre-filled syringes, blistering, and assembly of autoinjectors (pens), including serialization (track and trace).
The new drug substance site will be operational in November 2022 and will be starting process performance qualification for new products to be produced in June 2023. The commercial manufacturing using the new fill/finish line will start product transfer in Q3 of 2022 and begin cGMP manufacturing in June 2023.
To support this capacity growth, we had already been setting up new storage facilities that include areas for storage at –80 °C and rooms for freezing/thawing, mixing, and so on. We made significant effort to optimize these side processes, including material transport. With this expansion, we are again ensuring that IDT Biologika can support the entire value stream.
DA: This new expansion is at the German site. Is there anything analogous happening in Rockville?
UF: Yes, the expansion is at our site in Germany and is valued at €120 million. We are also stepping up capabilities in Rockville as well. That investment is focused on expanding our cell and gene therapy technologies so that we have the expertise to support our U.S. customers in this space.
DA: How important are the new storage facilities?
UF: A lot of the drug substances we manufacture must be stored at –80 °C. Some of the cell lines must be kept much, much colder than that. That is why we added a much larger storage capacity with the capability of going down to –80 °C, as well as spaces for the storge of cryo cell lines and for performing freezing and thawing processes. Combining the freezing and thawing capacity with our storage capacity optimizes our operations and is, we believe, a real advantage and differentiator.
DA: Can you explain why you are enhancing your capabilities from BSL-2 to 3?
UF: Most of the products that we manufacture are viral vaccines manufactured under BSL-2. BSL-3 is a higher safety class required for some products, such as the SARS-CoV-2 virus. The decision to invest in BSL-3 was driven by customer requests and the fact that IDT always tries to offer flexible solutions for our customers. It was actually extraordinary, because we were able to work with customers to build suites very quickly, and now we are able to manufacture BSL-3 pathogens, which then get inactivated and then filled on the BSL-2 line. We were able to get the BSL-3 suites up and running so quickly, because we upgraded existing BSL-2 suites with the necessary air conditioning systems and other design aspects. Of course, we also invested in extensive training of our personnel on how to properly handle these more dangerous organisms.
DA: Is the new commercial drug substance capacity going to use single-use or stainless steel, and how have supply-chain issues been managed for such key materials?
UF: All of our new drug substance commercial manufacturing uses single-use plastic. There was discussion during the pandemic about supply concerns around single-use and if it would be better to go back to stainless steel. We elected to stay with single-use, because we have an established, well-functioning system and a strong purchase department securing material supply.
Certainly, with regard to the supply chain, the relationships between IDT and suppliers are different than they have been in the past. Before, you could simply place an order. Today, you need to be very transparent and look very deeply on a day-to-day basis regarding what is needed and how to get it. That has been particularly important with respect to the manufacturing of COVID-19 products, where every day counts. We did have issues like everyone, but we were always able to solve with our network, customers, suppliers, and the government.
We have a very strong network with all sorts of suppliers for single-use components and means of transporting them. And we have invested in a stronger purchasing department that has a good view of the supply of single-use materials. One approach we are taking is to try to bring companies manufacturing single-use products to locate operations at our site, because we have space for them.
DA: How do you see this expansion fitting into the broader growth of IDT Biologika and your strategic goals going forward?
UF: This expansion is a next step in a series of investments. IDT has initiated a very clear growth path. Once this investment in additional drug substance and drug product capacity with enhanced visual inspection capabilities is completed, we will be investing in a big storage/logistics center at our site, because that is something really needed to improve our overall positioning as a topline CDMO. The new logistics center will provide additional storage capacity for unforeseen events and for managing products that require storage at different temperatures. Then, within the next five years, we plan to invest in a new quality control facility and new syringe lines.
DA: If you look forward a couple of years, do you see any disruptive events or inflection points on the horizon that could potentially shift IDT’s priorities or approach?
UF: It is difficult to predict what might happen. We certainly don’t want another pandemic, but I think not only IDT but the whole world is much better prepared. At IDT, we are focusing on more regional supply of our materials and raw materials. Positive disruptions could be the introduction of new technologies; RNA vaccines and therapeutics are a good example. The success was driven by the pandemic and certainly not expected before that. Today, there are many other RNA candidates in development targeting many different indications, from infectious diseases to cancer, that could create significant change and have a real impact.
At IDT, we see ourselves not only as a manufacturer of viral vaccines but also a global, leading CDMO for vaccines in general. In the future, we hope to grow the company with the vaccine market and expand our ability to support many different types of vaccines, as well as other therapeutic modalities where the technology overlaps, such as cell and gene therapies that leverage viral vectors.
