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Analytical Procedures for Quality of mRNA Vaccines and Therapeutics (Draft Guidelines: 3rd Edition)

Type of Posting: General Announcement
Posting Date: 02–Aug–2024
Input Deadline: 31–Oct–2024
Expert Committee: Biologics Monograph 3 – Complex Biologics & Vaccines

Proposed Title: Analytical Procedures for Quality of mRNA Vaccines and Therapeutics (Draft Guidelines: 3rd Edition)

Suggested audience: Suppliers and manufacturers of mRNA vaccine drug substances, contract manufacturing organizations, drug testing organizations, regulatory agencies, and QA/QC specialists.

Background and objective: For decades, messenger ribonucleic acid (mRNA) technology has been investigated as a platform for vaccines for influenza, Zika, rabies, and cytomegalovirus (CMV), generating substantial amounts of research and preclinical data demonstrating safety, efficacy, and versatility leading to multiple human clinical trials. When the COVID-19 pandemic emerged, vaccine manufacturers leveraged these research outcomes combined with their R&D and manufacturing expertise to rapidly develop vaccines using mRNA technology. As a result, the mRNA platform became the first modality to receive emergency use authorization and then approval for SARS-CoV-2 in the U.S. 

The mRNA technology is also being leveraged for development of treatments and vaccines for other emerging infectious diseases, cancer, therapeutic protein replacement, and genetic diseases. Although mRNA technology can target diverse conditions, most applications use similar development and manufacturing processes, applying similar analytical procedures for quality assurance and control.

Proposal and stakeholder engagement: USP and global stakeholders have identified a need for analytical procedures and best practices to support the assessment of common quality attributes of mRNA vaccines. A standard set of analytical methods would support vaccine developers, manufacturers, regulatory agencies, and national control laboratories worldwide by providing methods to help accelerate the development and release of safe and effective vaccines and guard against substandard and falsified vaccine products.  As a first step towards developing a procedural chapter on the testing of mRNA vaccines, USP’s BIO3 Expert Committee developed draft guidelines containing methods to support testing of mRNA quality attributes for drug substance. The 1st edition of the guidelines was released for public comment on February 2022.

In April 2023, the 2nd edition of the guidelines, which was updated to address public comments and incorporate donated methods, was published by USP to gather further feedback from stakeholders worldwide.  With the release of this 3rd version, USP has addressed a second round of public comments and integrated additional donated methods into the guidelines. Additionally, USP has conducted evaluations of methods for several critical quality attributes (CQA) and incorporated these methods into the draft guidelines.

For more information and to download the draft guidelines, please click here. For more information and to download the draft guidelines please click here.

We would like to continue to encourage submission of additional alternative methods and supporting documentation, including validation documents, related to the methods presented in the draft guidelines. 

Submitting your document

Please submit your supporting documents to USPVaccines@USP.org

USP contact information

For further information, please contact Sarita Kattel, Principal Scientist, USP Biologics, sarita.kattel@USP.org or USPVaccines@USP.org.

USP looks forward to continued engagement from industry, regulators, and other stakeholders.