Incorporating New Approach Methodologies

Despite the increasing power of non-animal approaches, the move towards their inclusion in pharmaceutical safety testing is slow, largely due to a lack of familiarity among regulators. A group of international experts offer solutions.

New approach methodologies (NAMs) represent a wide variety of chemical risk assessment methods. Approaches range from simple assays on isolated components of cells, to computational modelling, to experiments on whole human tissues maintained outside the body. Besides the ethical benefits, NAMs can pick up on serious adverse effects in humans that are missed in animal studies, such as human drug induced liver injury (DILI). They can also be more cost-effective and efficient than animal testing.

Despite these advantages, companies and scientists may be hesitant to use non-animal approaches to test new medicines. Since regulators are often unfamiliar with NAMs, regulatory guidelines tend to be focused around animal testing, and scientific requirements for NAM-based safety testing are less clear. As a result, scientists and companies may find it difficult to assess how to meet safety testing requirements using NAMs.

To address this issue, an international group of experts including ImmuONE’s Chief Scientific Officer Dr Victoria Hutter produced a series of ‘maps’. The maps were graphical representations of the safety requirements for each of four organ systems: the cardiovascular system, the respiratory system, the liver, and the central nervous system. The participants considered which NAMs could be used to meet the requirements. ImmuONE’s models were noted to be useful models for monitoring acute inhalation toxicity.

The final maps could help stakeholders confidently select appropriate NAMs for the safety testing of new medicines. With further development, the set of maps could be converted into interactive decision trees and expanded to cover more organ systems. This expert guidance could lead to increased use of NAMs, higher productivity in pharmaceutical companies, and safer medicines.

The experts also offered further suggestions that could encourage wider adoption of NAMs. They noted that although several prominent pharmaceutical companies (e.g. AstraZeneca, Pfizer and GlaxoSmithKline) use NAMs in preliminary studies, more transparency is needed between both regulators and companies to see developments in this space.

A possible solution would be for companies to specify to regulators which NAMs they used in safety testing. This could make regulators more familiar with NAMs and encourage the incorporation of NAMs into pharmaceutical safety testing guidelines.