Pharma 4.0: What are Industry Leaders Prioritizing in the Modernization of Pharmaceutical Manufacturing?

The pharmaceutical industry is at a pivotal moment, where advancements in manufacturing technology are set to redefine drug development and production. But the reality is that the move towards “pharma 4.0” requires a major shift, both ideologically and technologically, to adapt current processes to a framework that will automate much of today’s manufacturing. According to data collected as part of CRB’s Horizon Life Sciences report, 31% of industry players pointed to automation and digital transformation as key priorities for capital investment projects presently or in the near future. In a presentation at INTERPHEX 2025 titled The Future of Biomanufacturing, Peter Walters, fellow, advanced therapies at CRB, discussed additional results from the report that shed light on priorities in both the lab and on the production floor, including AI, automation, and continuous manufacturing.

The Shift Toward Continuous Manufacturing

One of the major themes driving innovation is the shift from traditional batch processing to continuous manufacturing and the increasing integration of digital technologies. This transformation is driven by the need for greater efficiency, cost reduction, and improved product quality.

Continuous manufacturing not only accelerates production but also allows for real-time quality control, reducing waste and ensuring more consistent product quality. According to the survey data, more than 75% of respondents are currently using or plan to implement continuous technologies within the next 5 years, including in cell seed/expansion, filtration, solution prep, and chemical/enzymatic reaction, among others.

“When we think about continuous manufacturing, where you’re really getting that quality product is when you can achieve a robust process that's running at an equilibrium; you've got very good control over that whole state,” Walters said during the presentation. “Your protein is coming out of the bioreactor much faster, so instead of a traditional batch where the protein is sitting in the bioreactor for 14 to 20 days, here it's coming out daily, so it's not sitting in all that byproduct...before it gets processed. It's getting purified in real time, and you're getting a higher quality product [and] you're getting better control over that product stream.”

A Cautious Adoption of AI

Beyond continuous manufacturing, companies are investing heavily in artificial intelligence (AI) and data analytics to enhance their production capabilities. These technologies enable predictive maintenance, process optimization, and enhanced supply chain management, ultimately leading to faster drug development cycles. One key area of development and steep adoption is in inline sensor technology for real-time batch release and analysis, with a reported 40% indicating they use this now and an additional 38% planning to implement it in the next five years, according to the survey data.

About 85% of respondents indicated they were at some stage of planning or execution of the integration of AI in process data analysis in cGMP manufacturing, though there is still a great deal of caution around AI implementation in areas highly scrutinized by regulatory bodies, such as batch records.

“I know for some people the idea of AI in a cGMP-regulated setting could be a little unnerving, but it doesn't mean that we're handing over the sole finish to our robot overlords; it's a lot more like mechanical systems that have AIs on board to moderate themselves and look for mechanical issues in advance of them happening,” Walters explained. “I think where we also are seeing it is where you've got manufacturing steps that have to have very complex decision trees; you're still having a person make those decisions, but you're having AI models that can support that decision-making.”

Sustainability and Green Manufacturing

Another crucial topic was the industry's responsibility to adopt sustainable manufacturing practices. With rising global concerns about environmental impact, pharmaceutical companies are exploring ways to minimize waste, reduce water consumption, and lower carbon emissions. But how do those efforts fit in with the move towards continuous manufacturing?

“The whole idea about continuous biomanufacturing, ie., higher productivity and lower cost of goods, is a facility that's running constantly. Because it's continuously running, your HVAC, your lighting, and your whole infrastructure are running the same amount, but you're creating more product, so it actually is getting a better return on your facility investment,” Walters said. According to CRB, an energy model demonstrated that a continuous facility operates 33% more efficiently than one that runs a more traditional batch process.

Among the respondents, energy and waste were top priorities when it came to sustainability, but Walters was keen to point out the differences between companies prioritizing being carbon neutral versus those with net-zero goals.

“Carbon neutral a lot of times means [that] maybe [you] aren't even making any slight changes in how you do processing; you can buy carbon offsets, which means you're spending money towards things like fighting deforestation or putting in counter measures that help try to pull out greenhouse gas; things that are maybe off-site. Whereas net zero is where you're really trying to reduce what you're doing on-site. You are trying to recycle your waste, you're eliminating how much water you're using, you're putting in photovoltaic and more renewable power situations, and you're moving to a more electrified facility.”

But to no surprise, none of this happens overnight, and converting existing facilities to operate more sustainably is a tall order, Walters confirmed. Challenges can vary by company size, facility type, products produced, and other factors. Notably, more than 50% of respondents said that they currently have conservation practices in place to recirculate lab air, and more than 75% have on-site water reclamation/recycling currently implemented, in design, or planned to be implemented in the next 5 years.

Regulatory and Compliance Challenges

Despite the promising innovations, concerns about regulatory compliance and acceptance run rampant. The industry must navigate evolving guidelines from the FDA and the European Medicines Agency (EMA), ensuring that new technologies meet stringent quality and safety standards—a challenge that requires proactive engagement with regulators.

However, Walters was quick to point out that some of the fears about regulatory acceptance may in fact be imagined.

“FDA did an internal audit comparing traditional batch submissions to fully end-to-end continuous submissions, and they found that on average, application approval was 3 months faster for continuous and 4 months faster post-submission to market,” Walters said, challenging the general thought that regulators are a major hurdle in the switch from traditional batch to continuous manufacturing.

Looking Ahead

As the pharmaceutical manufacturing landscape continues to evolve, companies that embrace digital transformation, regulatory innovation, and sustainable practices will be best positioned for success. The presentation underscored the importance of collaboration between industry players, regulators, and technology providers to drive meaningful progress.

Recognizing that the biggest hurdle to adopting these new practices comes down to investment—not just monetary but time—Walters pointed out that startups are in a unique position to help push this technology forward, as they aren’t faced with the same hurdles of converting legacy sites and other large infrastructure burdens that larger, more established manufacturers face.

With significant change on the horizon, it’s critical that pharmaceutical manufacturers continue to adopt new technology and identify opportunities for innovation and efficiency in their processes.

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