In the wake of the pandemic, scientists are urging regulatory agencies to address safety concerns related to the swift approval of COVID-19 vaccines and to accurately classify messenger RNA (mRNA) vaccines as gene therapy products (GTPs). Failure to do so may allow pharmaceutical companies to bypass necessary regulatory standards.
A recent paper published in Nature on June 22 argues that COVID-19 mRNA vaccines should be categorized as gene therapy products due to their mode and action. However, U.S. and European regulatory agencies have not classified these vaccines as such, resulting in their regulation as vaccines for infectious diseases rather than being subjected to more rigorous GTP regulations.
Current regulatory guidelines either do not apply to RNA therapeutics, do not mention them, or lack widely accepted definitions for these products. As a result, regulatory agencies adopted a modified and accelerated approval process known as a “rolling review” for COVID-19 vaccines. Rolling reviews allow data to be evaluated as it becomes available, without requiring a complete data package or specific controls.
This expedited process led to the widespread administration of mRNA COVID-19 vaccines without thorough studies on their biodistribution, resulting in noncompliant results regarding purity, quality, and batch homogeneity. Manufacturers are now considering replacing conventional vaccines with mRNA vaccines, starting with influenza vaccines, using the same accelerated process.
The Centers for Disease Control and Prevention (CDC) currently defines a vaccine as a preparation used to stimulate the body’s immune response against diseases. However, the definition was changed in 2021 due to concerns that it did not encompass COVID-19 vaccines. Traditional vaccines contain antigens that trigger the immune response, whereas mRNA vaccines from Pfizer and Moderna do not.
Instead, the active substance in these vaccines is mRNA, the genetic material of the SARS-CoV-2 virus that provides instructions to the body for producing spike proteins, which act as antigens. The mRNA is translated into protein by the vaccinated individual’s cells, and their immune system generates its own antigens to trigger an immune response.
The U.S. Food and Drug Administration (FDA) acknowledges that mRNA is considered a gene therapy product. Furthermore, the FDA defines gene therapy as the modification or manipulation of gene expression for therapeutic purposes. The prodrug property of mRNA vaccines suggests that additional controls should be applied beyond those required for conventional vaccines. However, neither the FDA nor the European Medicines Agency (EMA) have referenced these qualifications for mRNA COVID-19 vaccines.
Dr. David Wiseman, a research scientist, explained that mRNA vaccines instruct the body to produce the antigen, making them similar to prodrugs that guide the body to generate the desired therapeutic effect. However, the FDA excluded vaccines for infectious diseases from gene therapy regulations, giving them their own set of rules. Nevertheless, Wiseman asserts that since mRNA COVID-19 vaccines meet the definition of gene therapy, they should be handled accordingly based on gene therapy guidelines.
According to the paper, because mRNA COVID-19 vaccines were not classified as gene therapy products, essential tests typically required for GTPs were not performed. These include assessments for genotoxicity, genome integration, germ-line transmission, insertional mutagenesis, tumorigenicity, embryo/fetal and perinatal toxicity, long-term expression, repeated toxicity, and excretion in the environment.
The authors argue that long-term safety monitoring should be conducted for mRNA vaccines, considering their persistence in the body and the expressed protein. Currently, safety monitoring for vaccines usually spans a few weeks, whereas GTPs require monitoring over several years.
The research paper highlights the need for proper classification and safety considerations for COVID-19 mRNA vaccines to ensure regulatory standards are met and potential long-term risks are adequately assessed.