Ensuring consistent high-quality mRNA drug product manufacturing under continually compressed timelines is a significant challenge for developers. Within this environment, the early identification of critical quality attributes (CQAs) reduces the risk of product development delays and ensures alignment of product quality testing and control with regulatory agency expectations.
However, mRNA is still a new modality with increasing knowledge and developing global regulatory guidelines, and there is still little precedent in terms of marketed products and regulatory approvals to help guide developers through the challenges associated with manufacturing and establishing quality control strategies. This situation could adversely impact control strategies and timelines and, in turn, increase the cost of batch product.
To help alleviate some of these issues, industry needs a resource of potential CQAs for products from the early stages of drug development to commercial manufacturing, enabling quick identification of relevant CQAs. This is why we have published Defining the Required Critical Quality Attributes (CQAs) and Phase Requirements for mRNA/LNP Product Development and Manufacture.
The paper includes a comprehensive list of the CQAs for mRNA/lipid nanoparticles (LNP), including the importance of testing at different stages of drug substance and product manufacture. A justification of the importance of each CQA is provided along with further information on whether these CQAs should be considered for a product – as there are many different mRNA products, each company will have its own in-depth understanding and specific characterization information to inform their specific quality control strategies.
“This paper represents the collective thinking of a broad spectrum of industry SMEs and leaders in the relatively new and extremely promising field of mRNA/LNP-based therapeutics,” said Steven Wolk, Vice President, Chemistry & Boulder Site Head, at Editas Medicine. “This work represents an initial effort to establish an industry standard for mRNA/LNP analytics that can be continuously improved through cooperation with the agencies, academia, and industry.”
It is important to note that various product quality attributes will be deemed critical based on regulatory guidance. So, the application of some or all of the CQAs must be assessed by the respective manufacturer in conjunction with the relevant regulator/authority. The CQAs in our paper may be considered potential CQAs, non-critical quality attributes or CQAs depending upon your individual product, process knowledge and legislative requirements.
We hope you find this paper a helpful reference while regulators continue to further develop and expand their guidelines. Considering these questions early on in the development of commercial manufacturing processes might also prompt you to consider measuring new CQAs or justify not including some CQAs to support efficient and appropriate quality control strategies.