Drug development in 2026: NAMs, safety and regulatory changes

As the pharmaceutical industry looks towards 2026, advances in New Approach Methodologies (NAMs) and shifting regulatory expectations are beginning to reshape how new therapies are developed and assessed. In a rapidly changing scientific and regulatory environment, drug developers are under increasing pressure to make earlier, more informed decisions without compromising patient safety.

To explore how these changes are influencing safety assessment, regulatory strategy and manufacturing, Drug Target Review spoke with Steven Bulera, Corporate Vice President and CSO for Discovery and Safety Assessment at Charles River and Matt Hewitt, Vice President and CTO of the Manufacturing Business Division at Charles River, on where the industry is heading and what it will take to get there.

Gradual integration into regulated spaces

NAMs are not about instantly replacing traditional animal studies in the regulatory space. Bulera is clear on this point: “This perception that we’re going to replace rat studies or dog studies or monkey studies completely next week is not going to happen. It’s going to be a small shift and it’ll take time.”

Despite this, NAMs are poised to play a transformative role in how pharmaceutical companies make early stage ‘go/no-go’ decisions.

“We’ve been doing in vitro work for decades, primarily, it’s been in two areas. One is to help develop drug efficacy models and the other is safety assessment,” said Bulera. “Many companies have panels to pick the best candidate for development using assays like phospholipidosis – all in vitro. That’s nothing new and that will continue. But with the advancement of organoids and microphysiological systems, the picking of compounds will only get better.”

The influence of NAMs is gradually expanding beyond the laboratory. Bulera sees that companies are increasingly employing a weight of evidence approach, integrating both in vitro and in vivo data to justify their development strategies. “We’re definitely starting to see an uptick in people using data, both in vitro and in vivo to create weight of evidence arguments,” he says. “This will influence decisions on how, or if, certain animal studies need to be conducted in drug development.”

Regulatory innovation: slow by design

Complementing the scientific advancements, regulatory innovation – or the lack thereof – has long been a critical factor in drug development timelines. Hewitt notes that regulators are traditionally methodical in their approach. “Regulators have always been slow to innovate and that’s by design. Do you want your regulator innovating? No – you want them regulating. But as technologies have caught up to our ideas the regulators are beginning to evolve as well.”

Hewitt also states that the current pace of technological advancement is unprecedented, which is challenging regulators to adapt rapidly. “We’ve had ideas on how to use these technologies for a long time, but we didn’t have the tools to implement them. Now we do and regulators are working to understand the ramifications and keep up. They’re starting to get on board.”

Navigating global regulatory complexity

One area where regulatory alignment is particularly complex is the international landscape. Hewitt points out that while harmonisation is a goal, it is challenging in practice. “We try to align with the US Pharmacopoeia, European Pharmacopoeia and Japanese Pharmacopoeia. But even then, there are differences. We see geographic separation where some regions move faster, which attracts companies. Once one region does it, others are somewhat forced to react.”

This dynamic highlights the growing importance of regulatory convergence – where global regulators align on standards and requirements to streamline development processes. While convergence is not uniform, Hewitt believes it will ultimately benefit the drug development ecosystem, particularly in rare and ultra-rare disease areas. “Time is probably the key resource here,” he notes. “Once it’s gone, it’s gone. An innovative, fast regulatory environment will attract interest and accelerate the development of therapies for patients in need.”

Real-world evidence: overcoming challenges in rare diseases

The goal, Hewitt stresses, is delivering new therapies to patients who currently have few or no options. “We can’t have patients waiting 15 years while we figure out how to develop a therapeutic in the traditional manner. Moving quickly is essential,” he says. “This is why regulatory innovation and real-world evidence initiatives are such a massive win, especially for rare indications.”

Real-world evidence (RWE) represents another area of transformative potential. Traditional randomised controlled trials can be infeasible for ultra-rare diseases, where patient populations are extremely limited.

“If you have 15-20 patients in the US and 20-30 in all of Europe, how do you build a randomised controlled trial with a rescue protocol? Rescue protocols are generally based on natural history studies, but in rare diseases, you can’t always construct those studies. RWE offers a path forward,” said Hewitt.

The impact of NAMs and weight of evidence approaches

The combination of NAMs, weight of evidence approaches and regulatory flexibility could significantly change the risk calculus in early drug development. While in vitro methods have long supported compound selection, the integration of advanced organoid systems and high-throughput assays is enabling more sophisticated assessments earlier in the process. This allows companies to make more informed decisions before moving into costly and time-intensive animal studies or clinical trials.

However, both Bulera and Hewitt caution that these approaches will evolve gradually. “The regulated space is not going to change overnight,” Bulera reiterates. “It’s going to be piece by piece. We’re seeing shifts, but they’re measured. Companies need to continue leveraging both in vitro and in vivo data to support their arguments.”

Accelerating drug development without compromising safety

Despite the steady pace, the impact on the industry is expected to be big. By enabling faster, safer and more precise decision-making, NAMs reduce the risk of late-stage failures, saving both time and resources. When combined with a forward-looking regulatory environment, this approach promises to accelerate the delivery of therapies to patients who need them most.

“We’re going to trip and stumble along the way, but the overall direction is positive. The reason we do this, ultimately, is to get new therapies to patients who have few other options. That’s what drives innovation and regulatory evolution in this space,” said Hewitt.

Combining new ideas with rigorous science

Both Bulera and Hewitt emphasise the importance of balancing scientific rigour with speed. While NAMs and advanced analytics promise better early decision-making, regulatory oversight remains crucial to ensure patient safety. The integration of these tools into established workflows requires careful planning, robust validation and ongoing dialogue with regulators.

Ultimately, the future of drug development lies in the interplay between technology, data and regulatory strategy. NAMs, real-world evidence and convergence initiatives are not just incremental improvements – they represent a shift in how therapies are discovered and delivered.

Looking forward: patient-centred change

“We’ve seen the power of integrating advanced in vitro models into our decision-making. The combination of these tools with robust regulatory frameworks will enable us to make safer, faster decisions,” said Bulera. “The ultimate goal is to reduce risk, accelerate development and get therapies to the patients who need them as quickly as possible.”

As the pharmaceutical industry navigates rapid technological advancement and evolving regulatory frameworks, the integration of NAMs, weight of evidence approaches and real-world evidence stands to make drug discovery more efficient and patient-centred. The next decade promises not only scientific breakthroughs but also a rethinking of how drugs move from discovery to delivery, ensuring that progress is matched by both safety and speed.

“At the end of the day, this is about patients. Faster innovation, smarter science and collaborative regulation mean therapies reach those who have no other options. That’s what makes this work meaningful and impactful,” said Hewitt.