The Future of Safer, More Predictive Drug Development

Expert Insights on New Approach Methodologies (NAMs)

The pharmaceutical industry is undergoing a significant shift toward New Approach Methodologies (NAMs) that employ systems engineered to closely reflect human biology, enhancing the relevance and predictive power of drug development.

In the webinar, NAMs and Regulatory Shifts Driving Safer, More Predictive Therapeutic Outcomes, our experts explore how NAMs are transforming translational research, enabling more predictive preclinical models, and aligning with emerging regulatory expectations.

Not watched the webinar? Watch on-demand now: NAMs and Regulatory Shifts Driving Safer, More Predictive Therapeutic Outcomes  

In the article below, we share key insights from the webinar discussion, addressing questions from the audience on regulatory timelines, emerging model systems, and the future of human-relevant biology in drug discovery.

To find out more about NAMs, visit NAMs – New Approach Methodologies.

Q&A: NAMs, Predictive biology, and the future of preclinical research

Who are our speakers?

Dr. Clive Roper has over 25 years of expertise in toxicology and has established himself as a leading figure in developing animal testing replacement technologies. His influence extends to board positions with organizations committed to replacing, refining and reducing animal testing, including the UK NC3Rs and the US 3Rs Collaborative.

Dr. Justyna Rzepecka is Associate Director of Immunology at Concept Life Sciences. Justyna has over 15 years of experience in immunology and cell biology, including more than a decade in drug discovery.

Dr. Hayley Gooding Biology Services Director at Concept Life Sciences is a dedicated and enthusiastic biologist driven by the art of problem-solving and building efficient solutions.

Q: Regulatory agencies are encouraging the use of NAMs. When might they fully replace animal models such as non-human primates?

Dr. Roper:

We are seeing clear regulatory momentum toward reducing animal testing, particularly in areas like monoclonal antibody development. Regulatory agencies are exploring strategies to replace or reduce the use of non-human primates (NHPs) where scientifically justified.

In the United States, the only information we have relates to the FDA statement and roadmap on mAbs and NHPs which seems to give 3-5 years. This only relates to mAbs and it is not clear what “and other drugs” refers to.

In Europe, we have the UK roadmap and policy paper which states “Target: We will aim to use validated alternative methods to reduce the use of dogs and non-human primates in dedicated PK studies for human medicines by at least 35% by 2030”, which is not an ending to the use of NHPs. The intention is to reduce the use, and where possible, replace with suitable testing strategies and methods. As we continue to build new tests, we will continue to find new ways to reduce or replace NHP use. In summary, we can envision some full replacement over the coming 5 years, but the end is further ahead.

The key takeaway is that this transition will be gradual, and evidence driven. As new tests are developed and validated, regulators will gain the confidence needed to incorporate them into regulatory frameworks.

Q: What is currently slowing the adoption of NAMs, and how can the transition be accelerated?

Dr. Roper:

Innovative assays and models are often successfully developed in academic or early research environments. However, the process required to validate them for regulatory use, demonstrating reproducibility, robustness, and predictive performance, is time-consuming and expensive.

There are many great tests being developed and there are usually good funding opportunities for this. One of the biggest barriers is what many refer to as the ‘validation gap’ which relates, in part, to validation which does not gain funding as it is not novel. This is understood and there is now interest in building funding for this process.

Regulatory agencies are looking at the criteria for tests for example, is there a legal mandate or a legal requirement, to use an animal to generate data on a particular health endpoint? Or, is the requirement for generating data on that endpoint? The former requires legal change, something that agencies have no power over, and the latter is interpretational, which could be changed more easily by an agency.

The former would need to be demonstrated to law makers. Of course, this only relates to regulatory testing and there are more animals used outside the regulatory space. This is down to funding bodies to make a change in their funding priorities or perhaps more flexible to accept alternative methods more quickly.

Q: How are advanced cancer models evolving within NAM frameworks?

Justyna:

Multicellular tumor models are becoming increasingly sophisticated, particularly as researchers attempt to recreate the complexity of the tumor microenvironment. Currently, the cancer-associated fibroblasts (CAFs) and immune cells in our multicellular cancer models are not isogenic with the patient sample. Our system primarily uses established cancer cell lines rather than patient-derived cancer cells.

We have begun incorporating primary CAFs obtained from cancer patients into these models to enhance physiological relevance. However, this approach introduces significant variability between patient samples and is constrained by limited availability and access to high-quality primary material, which can impact reproducibility and scalability.

In terms of throughput, the current assay format is performed in 96-well plates, but the platform is adaptable for higher-throughput screening if required. The overall goal is to strike the right balance between biological complexity and scalability, ensuring models remain both predictive and practical for drug discovery programs.

Q: Are pharmaceutical companies moving toward patient-derived cancer models for routine drug testing?

Justyna:

Yes, we are seeing growing interest from pharmaceutical companies in using patient-derived cancer models for routine testing, as these systems offer greater physiological relevance compared to traditional cell lines. This trend reflects the broader movement toward more predictive pre-clinical platforms.

However, there are significant challenges to address before widespread adoption. The most critical is tumor heterogeneity, both inter-patient and intra-tumor variability, which can profoundly impact drug response. To mitigate this, studies typically require larger sample cohorts to capture variability and identify robust response patterns. This introduces logistical hurdles, including access to sufficient high-quality patient material, ethical considerations, and the difficulty of re-testing on the same patient samples for reproducibility.

To address these challenges from a technical perspective, standardization of culture conditions and assay formats is essential to reduce variability. In short, the field is moving in this direction, but logistical, scientific, and scalability issues need to be solved to make patient-derived models a routine part of pre-clinical drug discovery.

Q: What role do iPSC-derived cells play in the future of NAMs?

Justyna:

Induced pluripotent stem cell (iPSC) technology offers a reproducible and scalable source of human cells, which is a major advantage for NAMs. They help overcome some of the availability challenges associated with primary cells, particularly for tissues that are difficult or impossible to source directly from patients.

As mentioned in the presentation, primary blood cells are readily available and provide strong translational relevance, but this is not the case for all organs. For example, in neuroscience, obtaining primary human neurons and glial cells is not feasible, so iPSC-derived cells have become essential for building human-relevant translational models.

At Concept Life Sciences, we already use iPSC-derived cells extensively in our neuroscience platforms and I see clear opportunities to expand their use into other therapeutic areas. That said, there are still technical challenges to manage, including:

• Achieving appropriate cellular maturation.
• Ensuring functional fidelity.
• Managing variability between iPSC lines.

This needs careful management through assay design and validation to ensure robust and predictive models.

Q: Are NAMs also being used in veterinary drug development?

Dr. Roper:

Adoption in veterinary toxicology is progressing more slowly than in human drug development, but there is growing interest. We are aware that veterinary drugs need to be tested in the relevant species (cattle, pigs, chickens), but this also is important for companion animals such as dogs and cats. This industry is looking for in vitro models before they go into their clinical trials.

The NC3Rs virtual dog project would help here. There are a number of animal in vitro models already developed in support of translation from animal to human to select the best species for (mandated) preclinical testing and to protect animal health by seeing what toxicities could be observed or in supporting dose level selection as part of 3Rs programs. These may be used in support of veterinary and companion animal health programs. The test method developers will work on developing these models, but they must see there is a business opportunity, and they need to get the tissues to create the models.

As veterinary health companies recognize the benefits of these models, we expect continued growth in this area.

Q: How do you ensure NAM models are predictive and reliable?

Hayley and Justyna:

Validation and benchmarking are critical components of model development. We have conducted validation work using reference compounds with known clinical outcomes across many of our model systems. This helps us assess the predictive performance and translational relevance of each platform.

Our standard practice includes incorporating positive and negative controls within assays to benchmark responses and ensure reproducibility. These controls provide confidence in the robustness of the models and allow comparison against expected pharmacological profiles. Some of this validation data is available on our website, and we continue to expand these datasets to strengthen predictability.

The Bigger Picture: NAMs and the Future of Drug Discovery

The transition toward NAMs represents more than a technological shift, it reflects a broader move toward human-relevant, data-rich, and ethically responsible drug development.

Advanced in vitro systems, computational approaches, and translational biology platforms are helping researchers:

• Improve predictive accuracy in early drug discovery.
• Reduce late-stage clinical failure risk.
• Align with evolving regulatory expectations.
• Support ethical and sustainable research practices.

As highlighted throughout the discussion, the journey toward full regulatory adoption will take time. However, the scientific and regulatory momentum behind NAMs is clear. Researchers and developers who adopt these approaches early will be better positioned to deliver safer, more predictive therapeutics faster.

Explore more:

Watch the on-demand webinar: NAMs and Regulatory Shifts Driving Safer, More Predictive Therapeutic Outcomes

Learn more about New Approach Methodologies and integrated testing strategies through the NAMs campaign resources