Previously on this blog, we have explored the 2020 Chinese export ban on non-human primates (NHPs) and its consequences on pharmaceutical research. In that same post, we explored potential solutions to keep sponsor programs on track.
In response to the NHP shortage and the resulting challenges within the industry, the FDA published a new guideline in February 2022 called Nonclinical Considerations for Mitigating Nonhuman Primate Supply Constraints Arising from the COVID-19 Pandemic: Guidance for Industry, which we have summarized below.
Two main issues are addressed: the development of biological products and the conduct of Development And Reproductive Toxicology studies (DART).
The FDA acknowledges the acute shortage of sexually mature NHPs, which are often the only pharmacologically relevant species for biological products (though in some cases sponsors may be able to offer a strong scientific rationale for using a non-rodent species other than NHPs). In the guidance, the Agency explains that it will now consider one-species-only toxicology programs to be scientifically supported, with general toxicology tests being conducted only in rodents, pending a well-researched rationale and on a case-by-case basis:
On a case-by-case basis, if the biological product is active in a rodent and acts on a well-characterized target (e.g., vascular endothelial growth factor, or its receptor), it may be scientifically appropriate for sponsors to conduct warranted general toxicity studies only in the rodent.
Along with generally reminding sponsors that NHPs were already discouraged for testing small molecules, the guidance discourages their use in the collection of DART endpoints in biologics programs. This is a divergence from the previously relevant guideline, ICH S6(R1)8:
Although the stated preference of ICH S6(R1)8 is for testing the clinical candidate (in the NHP), while the supply of NHPs is disrupted, we strongly encourage the use of appropriate alternative models for assessing DART endpoints (e.g., species-specific surrogates in rodents, genetically modified rodents) when scientifically justified.
The FDA also recommends using independent sources of relevant information in place of new studies and redesigning enhanced pre- and post-natal development studies with fewer test article groups. In addition, if products are not likely to be used by women of childbearing potential, the FDA has agreed to delay collection of DART endpoints until post-marketing studies.
Although we all hope that the pandemic will soon come to an end, we share the FDA’s expectation that the NHP shortage might continue past the official end of the COVID-19 public health emergency. With that in mind, this guideline will remain relevant for the foreseeable future. However, the FDA intends to revise and replace this guidance with appropriate changes no more than 60 days after the end of the COVID-19 public health emergency.
All in all, sponsors are encouraged to reach out early and often to the FDA for design input before executing any required studies – our regulatory experts at Premier Consulting can help to support these interactions with the FDA to get you the Agency buy-in you need to proceed.