USP Releases 3rd Edition Draft Guidelines for mRNA Vaccine and Therapeutic Quality Analysis

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USP Releases 3rd Edition Draft Guidelines for mRNA Vaccine and Therapeutic Quality Analysis

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USP Releases 3rd Edition Draft Guidelines for mRNA Vaccine and Therapeutic Quality Analysis

USP Releases Latest Revision: Draft Guidelines for Quality Analysis of mRNA Vaccines and Therapeutics (3rd Edition)

The United States Pharmacopeia (USP) has recently released the 3rd edition of its “Analytical Procedures for Quality of mRNA Vaccines and Therapeutics-Draft Guidelines.” Previous versions of these guidelines were published in February 2022 and April 2023.

For decades, mRNA technology has been under research as a platform for vaccines targeting diseases such as influenza, Zika virus, rabies, and cytomegalovirus (CMV), generating extensive preclinical and research data that supports its safety, efficacy, and versatility. This body of research facilitated rapid vaccine development during the COVID-19 pandemic, bringing mRNA technology to the forefront.

mRNA technology is also being explored for other emerging infectious diseases, cancer therapies, protein replacement therapies, and treatments for genetic disorders. Despite the diverse applications of mRNA technology, most of these uses involve similar development and manufacturing processes and utilize analogous analytical procedures to ensure quality control.

To address the needs of various stakeholders, USP and its BIO3—Complex Biologics and Vaccines Expert Committee have developed this draft guideline as an initial step towards standardizing mRNA vaccine testing procedures. This initiative aims to build public trust in innovative products like mRNA vaccines and therapeutics by ensuring their safety, efficacy, and quality. It also addresses the demand for a universal method to determine mRNA quality, which includes verifying the authenticity of active pharmaceutical ingredients, controlling impurities, and measuring the dose used in administration. This set of analytical methods is designed to support global developers, manufacturers, regulatory bodies, and national control laboratories.

The guidelines encompass analytical procedures and best practices to assess common quality attributes of mRNA vaccines and therapeutics. They are based on best practices outlined in the General Chapters of USP, including “Vaccines for Human Use—General Considerations” (<1235>) and “Vaccines for Human Use—Viral Vaccines” (<1239>).

Timeline of Guideline Development:

• February 2022: USP released the first edition of the draft guidelines, inviting feedback from global stakeholders. USP received over 300 comments, editorial suggestions, and donations of alternative methods, which were addressed in the second edition.
• April 2023: The second edition was released to gather further feedback. USP actively sought public comments on the revised draft and incorporated the suggestions and donated methods into the third edition.
• August 2024: The third edition is now available, reflecting public input and integrating several donated methods into the guidelines. USP has also evaluated various key quality attribute (CQA) methods and included them in the draft.

Key Updates in the New Draft:

1. Table 1 Update: The previous version of Table 1 has been replaced with a new version adapted from the proposed USP <1040> chapter published in the Pharmacopeial Forum (PF), the online platform for the establishment and revision of USP standards. This chapter, focused on the quality attributes of plasmid DNA as starting materials for cell and gene therapy, is currently undergoing a 90-day public comment period.

2. New Methods Added: The draft now includes donated LC-MS methods for assessing 5′ capping efficiency and 3′ poly(A) tail length.

3. Updated Methods:

   • Immunoblot method has been revised.
   • A step for detecting residual nucleoside triphosphates (NTPs) and capping reagents using anion-exchange high-performance liquid chromatography (AEX-HPLC) has been added to the mRNA analysis methods.

4. Method Evaluations by USP:

   • LC-MS method for detecting 3′ poly(A) tail length.
   • Immunoblot method for detecting double-stranded RNA (dsRNA) impurities.
   • AEX-HPLC method for detecting residual NTPs and capping reagents in mRNA.
   • Capillary gel electrophoresis (CGE) method for assessing mRNA integrity.
   • Ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC) method for evaluating mRNA purity.

To further support the quality and consistency of analytical methods in mRNA-based vaccines and therapeutics, USP has initiated evaluations in its laboratory to qualify and/or validate these methods. Some methods may be advanced as documentary standards (e.g., with validation methods) and will be made available for public comment in the Pharmacopeial Forum before inclusion in the USP-NF (United States Pharmacopeia–National Formulary) chapters. In other cases, due to the wide range of mRNA products under development, standardization may be more challenging, and the methods or relevant information might be published outside the formal inclusion process, such as in draft guidelines, technical notes, or scientific publications.

USP Releases 3rd Edition Draft Guidelines for mRNA Vaccine and Therapeutic Quality Analysis

References:USP—Analytical Procedures for Quality of mRNA Vaccines and Therapeutics-Draft Guidelines: 3rd Edition.

(source:internet, reference only)

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