The exponential technology disrupting the pharmaceutical industry is not what you think it is.
When you think of exponential technologies + the pharmaceutical industry, what comes to mind?
I bet it had something to do with cell and gene therapy, regenerative medicine or cancer treatments. Am I right?
In fact, the technology that is disrupting the industry more quickly than new drug therapies has nothing to do with what’s being made at all. It’s how drugs are being made.
So let me introduce you to….
🥁🥁🥁🥁
Continuous processing!
What exactly is continuous processing?
Categorizing continuous processing as an exponential technology is probably incorrect. Continuous manufacturing has already been employed in many industries for centuries.
Anti-climactic much?
In spite of this, the pharmaceutical industry is wedded to batch manufacturing. To understand the difference between batch and continuous manufacturing, think about the two different ways one could make donuts.
Every year on Christmas, my dad pulls out a donut maker from Williams Sonoma from the back of a cabinet we never use. After hand-mixing the flour, sugar and baking powder in a bowl, he pours the mixture into the 7 donut-shaped molds in the maker, shuts the lid, and lets them bake for a few minutes.
The donuts are always amazing, but it’s a time-intensive process that requires a lot of energy input for a small batch of 7 donuts.
Contrast this with an industrial-scale continuous process. Did you ever go to a Krispy Kreme factory growing up? Donut ingredients are fed into a machine that plops rows of donut mixture onto a conveyor belt. This bakes the donuts in hot oil on one side, flips them and bakes the other side, slides them through a steady stream of glaze and then shuffles the baked donuts into boxes.
The process may occur without human intervention after loading ingredients into the machine. An industrial donut factory can produce thousands of donuts per day through continuous manufacturing.
As it stands now, the drug manufacturing process has not changed much in the last 70 years. If you transported a chemical engineer from the 1950s to a pharmaceutical manufacturing plant today, they would recognize most of the process units (reactors, mixers, blenders, etc.).
Contrast this to what an electrical engineer’s experience would be if they were teleported into IBM today! But why stick with batch all these years? Such processes are the easiest to practice in the laboratory while being the simplest to understand and commercialize to produce the needed product.
On top of this, the pharmaceutical industry is slow to adopt new tech because it lacks sufficient competition, is highly profitable and ultra-conservative. As it stands now, only 4 drugs have been approved by the FDA to be produced using continuous manufacturing.
Why the big push towards continuous manufacturing?
The FDA chief Scott Gottlieb claims that continuous processing will “improve drug quality, address shortages of medicines, lower drug costs, and bring pharmaceutical manufacturing back to the United States.”
From an operational standpoint, switching to continuous processing has clear advantages.
Efficiency
The process eliminates, or at least significantly reduces, “hold times” between batch manufacturing steps. When Johnson & Johnson switched their HIV drug Prezista from batch to continuous, a process that once took two weeks now takes about three days to produce the same volume of drug.
Manufacturing times are shortened because product intermediates don’t need to spend time transitioning in and out of production for quality testing. This means that continuous processes can run over longer periods, and the increase in speed and agility is a huge driver for pharma companies to adopt this technology.
Agility
Continuous processing is also more flexible to respond to shifts in market demand for a drug. Instead of being wedded to a fixed-size batch, a company could decide to switch from a nine-hour run to a two day run with ease. Eliminating the need to increase the size and footprint of process units if demand for a drug surges, this can mitigate the current issues the industry is facing with drug shortages.
This also lends itself to an increased ability to develop a much wider range of doses without having to develop an entirely different process.
Environmental Sustainability
Environmental impacts are generally lowered with continuous processing. Because a process can potentially run 24/7, process unit size and scale can be reduced. This leads to a significant decrease in the energy, chemicals, and water used in the cleaning process, one of the most wasteful aspects of pharmaceutical production.
Sanofi, a pharma company in Massachusetts, successfully reduced its carbon dioxide emissions by 80%, water usage by 94%, and chemical usage by 91% by switching to a continuous manufacturing facility.
Safety
Finally, continuous manufacturing could also be safer, as it eliminates the transition steps where drug product needs to be handled and safely stored.
Continuous processing also makes the product safer for patients, as uniformity of quality of products is inherent in such a method of manufacturing.
In batch manufacturing, you might not know that there’s an issue with a batch until the very end when tablets are submitted for testing, and by that time, several other batches could have been produced and now must be disposed of. In continuous processing, sensors are incorporated throughout the line and are constantly monitoring the quality of the product in real-time. This decreases the chance of contaminated product reaching patients.
All of these improvements end up cutting costs for pharmaceutical companies, which, let’s be real, will be the main driver behind transitioning to new process development standards.
So what are we waiting for?
Technical and regulatory challenges are the two biggest barriers to the widespread adoption of continuous processing in the pharmaceutical industry.
One of the toughest technical aspects of implementing continuous manufacturing is the need for appropriate measurement and control systems. Process dynamics require raw material controls, process monitoring, and detecting and handling deviation in real-time to support real-time release testing. A process to trace the raw materials through to the finished product must also be developed and customized based on the drug being produced.
Even though the food and beverage industry has methods and controls to continuously monitor product quality, the typically low concentration of APIs presents a technical hurdle for pharmaceuticals. This requires the design of new types of sensors, model-based control, multivariate monitoring, and large database management for analysis in real-time. A predictive model needs to be built to define action limits and to automatically adjust process parameters to manage process deviation.
On top of this, the level of regulatory submission requirements and inconsistent requirements around the world makes it difficult for the pharmaceutical industry to make any significant changes to an approved process. Even so, the FDA released a statement earlier this year endorsing the switch to continuous processes, and the agency is expected to take significant steps in defining the necessary regulatory standards.
Nevertheless, industry experts still expect continuous manufacturing to take over the pharmaceutical industry. Adoption will start with process development for new drugs — especially in personalized medicine — followed by big pharma companies re-designing their processes for existing drugs, finally followed by multinational generic drug manufacturing companies.