Nonhuman primates (NHPs) are used in preclinical research because their genetic, immunological, and physiological profile resembles the human one closely enough for pharmacology and toxicology to translate. The high cost and limited availability of these animals work against that. Prisys Biotech uses non-naïve NHPs, also known as "used animals," which have previously been subjected to drug treatments. The approach lowers cost and puts animals already in the colony back into study, and it comes with conditions that have to be met before a study can use them.
The Benefits and Challenges of Using Non-Naïve NHPs
Using non-naïve NHPs, especially those previously exposed to protein therapeutics such as monoclonal antibodies, ADCs, fusion proteins, or peptides, brings both opportunities and constraints. Prisys Biotech's assessment covers three practical points:
- Cost-Effectiveness: Non-naïve NHPs can cost half as much as naïve animals, which changes what a study budget can cover.
- Immediate Availability: These animals are often readily available, unlike naïve NHPs which may require lengthy procurement times.
- Ethical Considerations: Reusing animals aligns with the 3Rs principle (Replacement, Reduction, and Refinement) in animal research, and the reduction side of that argument is set out in reducing the use of nonhuman primates in nonclinical safety assessments.
The use of non-naïve NHPs is not without its hurdles. Key challenges include the potential for hypersensitivity reactions, residual pharmacological effects, and regulatory concerns. To address these, Prisys Biotech applies stringent criteria and rigorous screening processes before an animal is assigned to a study.
Example decision tree for inclusion of protein non-naïve NHPs in subsequent studies with therapeutic proteins.
Screening and Selection Criteria
Prisys Biotech follows a defined decision process to establish the suitability of non-naïve NHPs for a specific preclinical trial. The logic matches selecting the ideal non-human primate for toxicology studies: the animal's history is read first, and its fitness for the new molecule is judged second. The process involves:
- Baseline ADA Screening: Assessing for anti-drug antibodies (ADAs) to minimize the risk of hypersensitivity. Baseline ADA screening in washed-out monkeys is the gate that comes first, because pre-existing antibodies can confound both the safety readout and the exposure data.
- Pharmacological Sensitivity Screening: Evaluating the animal's responsiveness to new drug candidates.
- Washout Periods: Implementing adequate washout periods to mitigate residual effects from previous treatments.
- Clinical Pathology Monitoring: Ongoing health assessments to ensure the animals are fit for new studies.
Applications of Non-Naïve NHPs
Non-naïve NHPs can be used in several research contexts, including:
- Exploratory Research: Developing preclinical models and tissue harvesting for in vitro studies.
- Toxicology and Safety Pharmacology: Conducting dose range finding (DRF) studies and single-dose toxicity assessments.
- Pharmacokinetics (PK) and Pharmacodynamics (PD): Used in non-critical, non-GLP pharmacology studies for regulatory submission, the kind of work that sits outside Good Laboratory Practice and answers exploratory questions.
Industry Practice and Open Questions
Prisys Biotech is involved with the IQ Consortium NHP Reuse Working Group, which surveyed 15 pharmaceutical companies, including AbbVie, Novartis, and Merck. The survey revealed that while the majority support using non-naïve NHPs under specific conditions, concerns about hypersensitivity and regulatory rejection persist. Reliable ADA testing methods and detailed health records are what make the difference in that setting.
Conclusion
Prisys Biotech's approach to non-naïve NHPs in preclinical trials addresses two constraints at once: the cost per animal and the wait for supply. Used inside a screening protocol, these animals extend what a programme can do with the colony it already has. Reuse also keeps the 3Rs argument honest, since fewer animals enter the system for the same amount of data.
[1] Int J Toxicol. 2022 Aug;41(4):291-296. doi: 10.1177/10915818221101791. Epub 2022 Jun 2.
