The FDA has recognized the need to broaden its acceptance of a wider range of data types as part of the investigational new drug (IND) process and has been engaging with the community on this issue for many years. However, the lack of clarity in regulation has remained a barrier to industry investment in making the use of new alternative methods (NAMs) routine. The passage of the FDA Modernization Act provides assurance to pharmaceutical companies and creates opportunities for organ-on-a-chip technologies and other alternative testing models to be used in place of live animals. The legislation does not force pharmaceutical companies to adopt NAMs, but it creates opportunities for companies to consider other methods that weren’t acceptable before. The use of NAMs can reduce the use of animal models, lessen attrition rates and translation errors, account for diversity better, and ultimately bring safer and more effective medicines to the market.
The scientific community has been advocating for new alternative methods (NAMs) for preclinical testing for years. However, without clarifying legislation, many pharmaceutical companies were hesitant to invest in these new methods due to a lack of confidence that the data would be accepted by regulators. The passage of the FDA Modernization Act in late December 2022 is expected to change this.
The new drug application process requires pharmaceutical companies to submit preclinical data on their compounds before advancing into human clinical trials. Typically, companies collect and submit data from mice and larger animals such as monkeys, which has been the basis for IND approvals for many years. However, large translation gaps persist, leading to alarming attrition rates, including toxicological issues, poor replication of results in humans, and subpar efficacy profiles. Animal rights groups critical of the industry estimate that over 110 million animals are used globally in this research.
NAMs are crucial to addressing these gaps, and the FDA Modernization Act enables a new era for preclinical testing. It will provide assurance to the pharmaceutical industry that the data generated from NAMs will be considered in the investigational new drug process. This legislation is expected to accelerate the development of innovative and effective therapies while reducing animal use and costs associated with preclinical testing.
New alternative methods (NAMs) can help improve the understanding of how active ingredients in new drug products function in a human model, prior to their use in human testing. Examples of NAMs include cell-based assays, organ-on-a-chip technologies, computer modeling, and other micro-physiological systems. Approximately 90% of drug candidates entering human clinical trials fail, and NAMs can help improve the percentage of promising drugs entering these trials where the benefit to patients is illustrated and approval for the market is ultimately decided.
Another benefit of NAMs is the ability to better account for diversity in age, race, and gender/ethnicity across the human population compared to animal models. However, the lack of clarity in regulation has remained a barrier to industry investment in making the use of NAM-based methods routine.
The FDA has recognized the need to broaden its acceptance of a wider range of data types as part of the investigational new drug (IND) process and has been engaging with the community on this issue for many years. However, the agency’s interest was not enough to inspire change in the industry. In 2022, the FDA Modernization Act was passed, which provides the assurance the pharmaceutical industry has been waiting for regarding the use of NAMs in preclinical testing.
The FDA Modernization Act enables a new era for preclinical testing by broadening the acceptance of a wider range of data types, including NAMs, as part of the IND process. This legislation is expected to accelerate the development of innovative and effective therapies while reducing animal use and costs associated with preclinical testing. The FDA’s Alternative Methods Working Group cataloged the agency’s efforts within different offices to study NAMs, but this work served as more of a framework for regulators to draw on in evaluating data developed by NAMs rather than a clear roadmap the industry needed to broadly adopt these technologies.
In 2022, the FDA approved the first IND for a company testing a therapy for a neurodegenerative disease, which developed toxicology data using organ-on-a-chip technology in place of live animals. This was an important milestone for the industry because it showed that the data generated from NAMs could be acceptable to the agency for the first time. The passage of the FDA Modernization Act is expected to encourage the industry to invest in making the use of NAM-based methods routine, ultimately resulting in improved drug development and testing.
Pharmaceutical companies have been hesitant to adopt new alternative methods (NAMs) for preclinical testing due to the maturity of the field and a lack of clarity in law and regulation about whether these data would be accepted by FDA regulators. However, the passage of new legislation has brought clarity to companies, creating opportunities for organ-on-a-chip technologies and other alternative testing models to be used in place of live animals.
One of the most important components of the legislation is that it codifies the definition of a non-clinical test, which is needed for pharmaceutical companies to feel confident that their use of non-clinical testing methods will be acceptable to the agency as part of an investigational new drug (IND) submission. It also defines the types of animal testing alternatives acceptable as part of non-clinical tests, including specific animal testing alternatives such as cell-based assays, organ-on-a-chip models, and other methods.
The legislation does not force pharmaceutical companies to adopt NAMs or to transition away from animal testing, but it creates opportunities for companies to consider other methods that weren’t acceptable before. These incremental changes are critical next steps that will spur innovation and more experimentation using NAMs by the industry.
By adopting NAMs, the use of animal models can be reduced, attrition rates and translation errors can be lessened, diversity can be better accounted for, and ultimately safer, more effective medicines can come to the market for patients in need. However, it is important to note that NAMs are not a panacea and that they still have limitations that need to be addressed.
The passage of the new legislation is expected to accelerate the development of innovative and effective therapies while reducing animal use and costs associated with preclinical testing. It is an important milestone that brings much-needed clarity to the industry and creates opportunities for a new era of preclinical testing using NAMs.
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