Is the Pharmaceutical Industry Ready for Continuous Manufacturing?

Global pharmaceutical manufacturing — valued at more than $405 billion in 2020 — is expected to reach a compound annual growth rate (CAGR) of 11.34% by 2028. With increased consumer awareness and the COVID-19 pandemic spotlighting pharmaceutical drug development, there’s never been a better time to simplify processes, lower production costs and operate on a faster production-to-market schedule.

The global pharmaceutical industry has made strides with modern technology, but stringent standards and steep entry costs have left many U.S.-based manufacturers behind.

Could continuous manufacturing be the answer? Maybe — but only if the industry is ready to make some significant changes.

The State of Today’s Pharmaceutical Production

Recent years have shown the average consumer just how little pharmaceutical production occurs domestically. Outsourcing to other countries is an industry norm, but it became a point of contention at the height of the pandemic when production supply chains screeched to a halt.

American producers and consumers reflect the need for domestic pharmaceutical production. Companies benefit from production independence and consumers get faster, potentially more affordable access to critical medicines.

The pharmaceutical industry is slow to change, but not without good reason. Medication production is highly regulated for quality control. The industry has adopted many modern tools, like quality assurance management software (QAMS) and electronic batch manufacturing records (eBMR), but continuous manufacturing (CM) is a complete overhaul of drug production.

How Continuous Manufacturing Changes the Game

Pharmaceutical manufacturing has always relied on a batched manufacturing (BM) process, which breaks solid drug production into a step-by-step process with quality testing and storage between each step. Batch processing works, but it’s a slow process that leaves a lot of room for costly human error or contamination as production constantly starts, stops and moves through steps.

CM is an alternative method. Instead of processing ingredients in a step-by-step process, raw materials use vertically designed operations and gravity to create a nonstop end-to-end production stream for solid tablet and pill manufacturing. CM isn’t new — other industries have used it for decades — but it’s still an early concept in pharmaceuticals. As of 2021, only about eight approved drugs have been produced through CM methods.

Compared to BM, CM gives real-time insights into manufacturing data to improve product quality and catch issues before too many resources are wasted. CM also involves fewer human contact and transition steps, reducing safety and contamination risks.

Early CM adopters have found the following benefits:

• Sustainability: CM manufacturing is easier to scale while simultaneously reducing facilities’ industrial footprint. Facilities consume less water and resources because there are fewer parts to clean between batches. CM can also create a more sustainable job market in pharmaceuticals. Fewer hands are needed during production, but CM facilities need IT specialists and R&D personnel to understand datasets.
• Speed: Fewer production pauses and material transitions mean medicine reaches the consumer faster. CM facilities are also smaller and easier to establish than traditional batch facilities, creating even faster turnaround times.
• Control: A single production chain without interruptions lends itself to better process control, and real-time insights give manufacturers a closer look at all steps being taken. Uniformity and consistency are nonnegotiable in pharmaceuticals, and CM makes that easier to achieve.
• Innovation: Industrywide CM adoption is a long way off, but it will pave the way for even more innovations in the future, such as personalized medicines and on-demand production.

Barriers to Entry Keep Widespread CM at Bay

The benefits of CM for pharmaceutical manufacturing are clear, but steep barriers to entry prevent it from becoming the new industry standard in the U.S.

Widespread CM is a possibility, but not an immediate one. Here’s why:

1. Lack of Regulatory Precedent

CM processes are common in other industries, but the pharmaceutical sector has no precedent to follow, meaning there is no uniformity in regulation or industry guidelines. Lack of regulatory precedent means product approval could be harder to get, leading to further delays.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is a work-in-progress set to establish official guidance. Other bodies, like the World Health Organization (WHO), remain unchanged.

2. High Initial Costs

CM can potentially lower pharmaceutical production costs in the long term, but the initial expense is too costly for many producers. There’s a lot of uncertainty that comes with no industry precedent to follow and no government funding allocated toward CM investments.

Facilities would have to replace traditional batch processing machinery with CM equipment and automation software, as well as trained specialists who know how to operate them.

3. Not Enough Research

Early CM adopters report tighter quality control during production. However, there is little research surrounding the long-term quality of the CM’s final product and possible impacts on drug efficacy, safety or the generic market.

The investment might not be worth the additional risk without a formal benchmark to measure production quality. That said, early CM adopters in pharmaceuticals are experimenting with its capabilities and testing the waters to determine what works and what doesn’t. That makes future CM adoption far less precarious.

4. Physical Limitations at Manufacturing Facilities

CM changes might also include structural adjustments to the facility itself to accommodate new equipment, especially if there isn’t enough vertical space overhead.

Current manufacturing processes create natural downtime between batches, allowing plenty of time to break equipment down for cleaning, inspection and sensor calibration. CM’s nonstop production is certainly an asset for production, but developers must create a feasible maintenance solution.

Making Continuous Manufacturing a Reality in Pharmaceutical Production

The benefits of CM could outweigh these barriers to entry, but it’s going to take significant industrywide changes to make it a reality, such as:

• Incentives: Financial and regulatory incentives, like tax breaks or exclusivity periods, could be the final piece for manufacturers on the fence about switching to CM.
• Regulatory clarity: Regulatory clarity and a set of uniform international CM standards specifically tailored toward pharmaceutical production would decrease the uncertainty that stops many from investing.
• Equipment advancements: Equipment will also need to meet new chemistry flow needs and the ability to integrate with future technologies. Flexible CM machinery that meets multiple production needs and works with an interchangeable facility layout — like modular pieces — would make the investment less risky. It could also let some manufacturers output multiple drug types from a single facility.
• Process transformation: Switching from BM to CM involves many process changes, including digital transformation on various scales, depending on the manufacturer. Lab systems must accommodate new volumes of data and work with advanced predictive technologies and cloud storage for optimal efficiency.

CM Will Transform Pharmaceutical Production — but Not Yet

Despite significant barriers to entry, widespread CM adoption could be just what the pharmaceutical industry needs for faster, high-quality production and less reliance on outsourced materials and processes.

For now, some pharmaceutical companies could strike a balance between tried-and-true batch processing and more efficient CM-driven processes through a hybrid approach. Combining elements of BM and CM lets them expand capabilities with much smaller risk and initial investment.

A hybrid approach lets manufacturers ease into new processes and experience CM’s cost and output benefits firsthand while paving the way for larger industrywide changes in the future.

Emily Newton is the Editor-in-Chief of Revolutionized, a magazine exploring how innovations change our world.