The rise of messenger RNA (mRNA) technology has transformed the pharmaceutical industry, as shown by its recent creation and use during the COVID-19 pandemic. mRNA therapeutics use synthetic RNA molecules to direct cells to make specific proteins that can prevent or treat illness, unlike conventional drugs that deliver protein directly to the body. mRNA serves as a guiding tool letting the body make the desired protein on its own. The immune cells recognize the protein as a foreign substance and launch defenses against it. The mechanism extends beyond vaccines, as the same methods are also being used in cancer treatment, where mRNA can instruct the cell to produce proteins that trigger an immune response against cancer cells.
Regulatory Framework for mRNA-Based Therapeutics
Currently, there are no mRNA-specific guidance in the USFDA and EMA. World Health Organization’s (WHO) “Guidelines for assuring the quality, safety, and efficacy of plasmid DNA vaccines” serve as the basis for the development of mRNA-based vaccines.
In the U.S., the FDA’s Center for Biological Evaluation and Research (CBER) oversees mRNA products as biologics. The regulatory pathway includes:
Investigational New Drug Application (IND): Sponsors must submit an IND application to the FDA before they start human clinical trials. This application includes data from the preclinical studies that show the drug is safe and effective.
Biologics License Application (BLA): After successful clinical trials, a BLA is submitted to request approval for commercial distribution. This application includes comprehensive data from preclinical studies, clinical trials, and manufacturing processes.
Emergency Use Authorization (EUA): During the global health emergency, like the COVID-19 outbreak, the mRNA vaccine got EUA. The FDA gave approval based on early proof that the vaccine was safe and effective.
The European Medicines Agency (EMA) establishes regulations in the European Union (EU). The regulatory framework for advanced therapy medicinal products (ATMPs) includes gene therapy and somatic cell therapy medicinal products, with mRNA-based products classified based on their intended use.
A Clinical Trial Application (CTA) is required for conducting clinical trials in the EU. Manufacturers must submit a Marketing Authorization Application (MAA) after successful trials to obtain permission to market the product in the EU, requiring extensive data on quality, safety, and efficacy.
Both the FDA and EMA provide expedited medical pathways for urgent medical needs, with the FDA offering designations like Breakthrough Therapy, Fast Track, and Priority Review, while EMA offers similar options like the PRIME scheme and accelerated assessment.
mRNA clinical trials must follow strict rules with Institutional Biosafety Committees (IBC) overseeing the studies that involve engineered material recombinant or synthetic nucleic acid molecules, including mRNA. Established under the NIH Guidelines, IBCs provide local review and oversight to ensure that research complies with safety regulations and ethical standards.
The most outstanding success of mRNA technology is the development of the COVID-19 vaccines. BioNTech-Pfizer and Moderna produced one of the first COVID-19 mRNA vaccines. The FDA granted an EUA based on clinical trials and substantial evidence.
Conclusion
The regulatory frameworks will need to evolve with the advancing mRNA technology. Researchers are conducting studies to tackle issues like stability, storage conditions, and toxicity related to mRNA-based therapeutics. mRNA-based drugs will be used to treat genetic disorders by instructing cells to produce missing or defective proteins in the near future.
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In addition to providing regulatory and pharmacovigilance services for global customers, DDReg Pharma offers specialized clinical regulatory services to assist with Clinical Trial Applications in Europe. For further information, connect with our experts. Read more about EU regulations from the experts here: Expediting Access to Cell and Gene Therapy Products