Michele Duggan is senior manager, Regulatory Affairs, at Thermo Fisher Scientific.

Michele Duggan

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The development of effective vaccines to combat COVID-19 has showcased the potential of messenger RNA (mRNA) technology, which is now under exploration for various clinical areas, including oncology, HIV, rare diseases, and personalized medicine. Given that the application of mRNA technology is relatively new, regulatory guidelines and industry standards that address specific aspects of mRNA quality during process development are still evolving, with existing resources primarily focused on mRNA vaccines.

Navigating an Uncertain Regulatory Environment for mRNA-based Products

How this guidance will translate for developers of mRNA products for other therapeutic modalities remains to be seen. Developers will need to remain nimble during this period of evolution and stay aware of emerging regulatory guidelines applicable for their unique therapies. Collaborating with a strategic contract development and manufacturing organization (CDMO) partner that has the appropriate industry knowledge and experience can help developers navigate these challenges and bring novel mRNA products to market faster.

Current and developing regulatory guidance for mRNA products

mRNA-based products are currently regulated within existing frameworks of both FDA and the European Medicines Agency (EMA). FDA oversees mRNA-based products under its Center for Biologics Evaluation and Research (CBER), and the responsible review division is assigned based on indication (e.g., vaccine, oncology). In Europe, mRNA-based vaccines can fall under different regulatory statuses depending on their target (infectious disease or not).

The regulatory framework for advanced therapy medicinal products (ATMPs) includes both gene therapy medicinal products (GTMPs) and somatic cell therapy medicinal products (sCTMPs). mRNA-based products may be classified under either category, depending on their intended use.

To help navigate the regulatory complexity in Europe, the Committee for Advanced Therapies, an advisory committee that reports into EMA, provides non-binding opinions including classifications of ATMPs. This legal status is critical to understand as it can have implications for different controls and other specificities that are intended to limit risks for different product types.

Navigating a region’s regulations can be challenging and sometimes cause for confusion. Guidance documents serve an important role in providing industry with the health authority’s interpretation of policy on a regulatory issue while not being legally enforceable. Naturally, guidance documents become an important part of the region’s regulatory framework. The process for the development and issuance of guidelines is based on policy itself, involves public consultation, and can be quite lengthy.

specific guidelines related to chemistry, manufacturing, and control (CMC) considerations for mRNA-based products. Past guidance documents issued by FDA, such as the 2018 FDA final guidance document on liposome drug products and the 2022 final guidance document on drug biological products containing nanomaterials, offer some regulatory insight to mRNA developers that employ liposome delivery strategies, but these guidelines are written broadly and are not specific to mRNA (1,2).

The integration of mRNA-based vaccines into clinical and market settings during the COVID-19 pandemic highlighted the need for a collaborative approach to standardize quality expectations, facilitating their successful development. Early efforts are focused on vaccines for infectious disease, but undoubtably there will be principles and considerations that will be relevant to other mRNA therapies.

When referring to this article, please cite it as Duggan, M. Navigating an Uncertain Regulatory Environment for mRNA-based Products. 

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