Historically, biopharmaceutical manufacturing has always been slow, expensive, and inflexible. However, the pressures in today’s biopharma space are driving trends in the opposite direction, which is causing experts to look for ways to drive costs down while improving flexibility and efficiency. GSK’s Randy Maddux, VP and Site Director of the company’s Global Manufacturing and Supply (GMS) site in Rockville, believes there are many factors involved in transforming biopharmaceutical manufacturing. And while single-use technology plays a key role, there are plenty of other aspects to consider.
Planning For the Overall Product Life Cycle
|Randy Maddux, VP and Site Director of GSK’s Global Manufacturing and Supply (GMS) site in Rockville|
“Some people view disposable manufacturing as a panacea. I don't. I view it as a tool—as one thing that should be part of your strategy but not a strategy in itself,” explains Maddux. “When we look at the global market, two-thirds of the market or the patient base is in India and China. If you look at the income levels, especially those in India, there are not many people there who are going to be able to afford a $20K or $30K or $40K a year treatment regimen. If you really want to be a global player and get access to the patients that need your drugs, you're going to have to make a change in terms of your cost of goods for the big molecules. That's another piece of the equation.”
So, with so many pieces involved in the overall product life cycle, how do you manage and plan your manufacturing strategy? “In the beginning, when you have low volumes and high demand uncertainty, it makes sense that your big concerns are going to be around your flexibility and your speed to respond,” says Maddux. “As the product matures, you need to determine if you’re going to scale out, which means essentially running more small reactors, or scale up, which means running fewer, larger reactors.” This, of course, depends on the potency of the molecule and/or the titer the process is producing. Higher potency/titers offer the ability to use multiple small, single-use reactors, which provides flexibility when it comes to classifying and operating a facility, enabling rapid change from one product to another, and reducing operating costs in terms of maintaining the environment. At lower potency/titers, single-use does not make as much sense since a larger, stainless steel reactor is needed to produce larger amounts of a product. Maddux adds about the impact of titer, “If R&D can continue to improve on process titers and the potency of the molecules, you could literally see where you wouldn’t need the large scale facilities in the future.”
GSK’s Green Chemistry Commitment
Smaller tanks in the facilities of the future with fully-closed systems, or at least partially closed systems, have the potential to significantly reduce gowning and monitoring requirements, which currently create serious energy consumption issues. While process efficiency should be a top consideration for the sake of cost reduction, Maddux says GSK’s long-term plan for energy efficiency in GSK facilities also offers the potential for significant cost savings. “With respect to our utilities, we spend a lot of money and resources to obtain pharmaceutical grade water and steam to do our cleaning, our sterilization cycles, and to run our chillers,” says Maddux. “As facilities become smaller, both in scale and general size, they will become much more energy efficient. Our goal at GSK is to eventually become completely carbon-neutral in our manufacturing cycle.”
This long-term goal is part of GSK’s “green chemistry commitment,” which outlines a plan to be carbon neutral by 2050. The first step in this effort was taken in 2012 when GSK collaborated with the University of Nottingham to establish the GlaxoSmithKline Carbon Neutral Laboratory for Sustainable Chemistry, which is built using natural materials and supported by energy using renewable sources such as solar power and sustainable biofuel.
The Role Of Regulators
In order for the biopharmaceutical industry to transform and keep pace with demand, the ability for it to be innovative is a crucial factor; however, it is well known that the pharma community is very slow to change. The products produced are highly complex. Even changes to processes or equipment that may seem minor can have such an impact that a manufacturer could find themselves in a delay for regulatory approval, resulting in the loss of time, money, and even the ability to make and distribute their product. Maddux says these potential issues are often what keep companies from stepping outside of the box. “FDA expects us to be flexible and innovative in order to meet the needs of the patient while also ensuring our products are safe, effective, and available,” explains Maddux. “These expectations mirror GSK’s commitment to compliance and active support of regulations that ensure the quality of our products and the safety of our patients and employees. The challenge is to meet these regulatory expectations even as the FDA continues to raise the bar. We tend to be cautious because there is risk when introducing new ways for innovation to occur.”
There may be ways to transform biopharmaceutical manufacturing in direct cooperation with governments and regulators. In a recent blog, Rob Wright, chief editor of Life Science Leader, discusses one solution that many in the industry are calling for—incentivizing drug development. He references the impact of the Orphan Drug Act (ODA) of 1983 as an example. The ODA offers a number of incentives, such as federal grants, development assistance, and waiver of the PDUFA filing fee. Prior to its enactment, the industry averaged fewer than one specialty pharmaceutical drug for rare diseases per year. Today, that number is at 13.
Whatever the solution, it’s clear the industry is changing and every manufacturer may soon face a sink or swim scenario. While regulation and innovation are often opposing forces, collaboration and education go hand in hand, which is why it’s important for experts to get together whenever possible to discuss new ideas and solutions. Attendees of this year’s Bioprocess International Conference and Exhibition will have the opportunity to do just that. The event is taking place in Boston at the Hynes Convention Center from Oct. 20-23, and Maddux is only one of many presenters who will discuss the changing landscape of the biopharmaceutical industry and what tactics and strategies can be deployed in order to prepare.