FDA issues new guidelines, accelerating the development of personalized medicine

On January 4, 2021, the U.S. FDA issued a recommended procedure for the new drug application (IND) of individualized antisense oligonucleotide (ASO) products. The guidance provides clear information about the early development and IND submission process, and is the first step for the FDA to work with those who are developing these personalized drug products.

Advances in scientific knowledge and drug development technology provide opportunities for new methods of drug development, including the development of drugs for the treatment of rare diseases. In recent years, these advances have promoted the development and approval of rare disease drugs. In the past eight years, the number of drugs (orphan drugs) approved by the US FDA for rare diseases has greatly increased.

For genetic diseases, recent tests and molecular diagnostic methods can help diagnose the exact cause of the disease. Therefore, the development of pharmaceutical products for specific genetic mutations has become a new demand. Usually, these rare diseases develop rapidly, and if left untreated, they may lead to premature death. The development of these "n of 1" therapies-designed for a certain patient, brings a series of challenges and considerations that are not available in the typical drug development process. First, this type of disease Often rapid development requires timely medical intervention. Therefore, development needs to be carried out very quickly to have the opportunity to help patients. Second, the drug discovery and development of these drug products are carried out by academic researchers, not by biopharmaceutical companies. These studies Personnel may be less familiar with FDA regulations, policies, and practices, and have less experience in interacting with FDA.

Atpresent, the development of personalized genetic drug products for antisense oligonucleotide (ASO) products is the most advanced. Therefore, the FDA issued the "IND Submissions for Individualized Antisense Oligonucleotide Drug Products: Administrative and Procedural Recommendations Guidance for Sponsor-Investigators" to enable the development of personalized drugs This emerging field becomes clear.

This guideline aims to provide those who are developing ASO products with suggestions on how to interact with the FDA and submit a regulatory declaration to the FDA. The guide covers the following points:

How to get feedback from FDA,
Expectations and procedures for submitting regulatory submissions to FDA;
Recommendations on the requirements of the Institutional Review Board (IRB) to review internal agreements;
How to obtain informed consent.

This new drug discovery model raises many ethical and social issues that need to be resolved throughout the process. For example, in this case, individuals and their families are often more like drug development partners than traditional trial participants. Therefore, it is very important to discuss with individuals and family members how to measure effectiveness. It is also important to ensure that individuals and family members understand the parameters for continuing to take study medications before emotions influence decision-making, and recognize that certain study medications may fail or cause unpredictable side effects.

The FDA recognizes that regulatory agencies need to work with these drug developers to provide reliable drugs to patients. The FDA expressed its willingness to participate in drug development as needed to meet these challenges. For example, for those who develop these drugs, it is important to further understand the necessary data and information that must be submitted to the FDA so that clinical testing can begin. The FDA is continuing to consider and further develop policies to address some of these issues.

The FDA is also optimistic that the development of these personalized drug products may stimulate gene sequencing, thereby driving the development of other personalized drug products for the same disease (although it may be caused by different mutations). For this drug development method, the FDA needs to work with developers to determine how to effectively bring these drugs to those who need them.